Carcinoma, Renal Cell
Conditions
Keywords
Renal Cell Cancer, RCC, Cancer
Brief summary
The purpose of the study is to: * Find out if patients receiving BAY43-9006 will live longer without tumor progression than those receiving standard therapy with interferon alpha-2a * Find out if a higher dose of BAY43-9006 can inhibit tumor progression in patients who progressed during standard dose treatment with BAY43-9006, and for how long these patients live without progression * Find out how long patients live without progression who receive BAY43-9006 after failing to respond to standard therapy with interferon alpha-2a * Find out in how many percent of patients BAY43-9006 prevents the growth of or shrinks kidney tumors and/or their metastases depending on treatment and dosage * Find out if BAY43-9006 has any effect on the quality of life of patients with kidney cancer * Find out the level of BAY43-9006 in the blood once per month and any changes in this level * Find out whether BAY43-9006 effects are associated with specific biomarkers
Detailed description
Analyses on Biomarkers were exploratory and assessed as tertiary objective of the trial.
Interventions
DRUGSorafenib (Nexavar, BAY43-9006)
Multi kinase inhibitor
DRUGInterferon
Interferon
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who give written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, without prejudice * Male or female patients \>= 18 years of age * Patients who have a life expectancy of at least 12 weeks * Patients, who suffer from unresectable and/or metastatic, measurable predominantly clear cell RCC (Renal Cell Carcinoma) histologically or cytologically documented * Patients must have undergone prior (at the time of primary diagnosis) complete surgical excision of primary RCC tumor * Patients must have had no prior systemic therapy for advanced RCC. Prior systemic therapy is defined as any treatment with a chemotherapy agent (or regimen), an immunotherapy agent (or regimen) or an investigational treatment agent (or regimen) against the renal cell carcinoma. Megestrol acetate or medroxyprogesterone will constitute as a prior systemic therapy * Patients who have at least one uni-dimensional measurable lesion by CT (Computed tomography)-scan or MRI (Magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST) * Patients who have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 or 1 * Adequate bone marrow, liver , and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening * Hemoglobin \>9.0 g/l * Absolute neutrophil count ( ANC)\>1,500/mm3 * Platelets\> or = 100,000/ul * Total bilirubin \< 1.5 x the upper limit of normal * ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) \< 2.5 x upper limit of normal (\< 5 x upper limit of normal for patients with liver involvement of their cancer) * Amylase and lipase \< 1.5 x the upper limit of normal * Serum creatinine \< 2.0 x the upper limit of normal * PT (Prothrombin Time) or INR (International Normalized Ratio) and PTT (Partial Thromboplastin Time) \< 1.5 x upper limit of normal (patients who receive anti-coagulation treatment with an agent such as warfarin or heparin will be allowed to participate. For patients on warfarin, close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement at pre dose, as defined by the local standard of care)
Exclusion criteria
* Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta \[Noninvasive papillary carcinoma\], Tis \[Carcinoma in situ: flat tumor\]&T1 \[Tumor invades subepithelial connective tissue\]) or any cancer curatively treated \> 5 years prior to study entry * Complete renal shut-down requiring hemo- or peritoneal dialysis * History of cardiac disease : congestive heart failure \> NYHA (New York Heart Association) class 2: active cardiovascular disease( MI (Distant metastasis) more than 6 months prior to study entry is allowed); cardiac arrhythmia requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension * Active clinically serious bacterial or fungal infections (\>= grade 2 NCI-CTCAE (National Cancer Institute-Common Terminology Criteria for Adverse Events), Version 3) * Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C * Symptomatic metastatic brain or meningeal tumors unless the patient is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to this brain tumour site at the time of study entry. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies (head CT or MRI at screening always required) * Patients with seizure disorder requiring medication (such as steroid anti-epileptics) * History of organ allograft * Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results * Known or suspected allergy to the investigational agent or any agent given in association with this trial * Any condition that is unstable or which could jeopardise the safety of the patient and his/her compliance in the study * Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control (DC) According to Independent Central Review for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes. |
| Disease Control (DC) According to the Investigator Assessment for the First Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks | Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes. |
| Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks | Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes. |
| Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions: I have been short in breath and I have been coughing; its score ranges from 0 to 8. |
| Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions: I have been short in breath and I have been coughing; its score ranges from 0 to 8. |
| Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. |
| Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. |
| Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL. |
| Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL. |
| Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. |
| Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. |
| Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. |
| Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. |
| Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. |
| Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. |
| Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. |
| Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks | Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation |
| Tumor Response According to the Independent Radiological Review for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes. |
| Tumor Response According to the Investigator Assessment for the First Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks | Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes |
| Tumor Response According to the Investigator Assessment for the Second Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks | Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes |
| Progression Free Survival According to the Investigator Assessment (Second Intervention Period) | From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks | Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation |
| Overall Survival (OS) | From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks | Overall Survival was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact |
| Slope - Change in Trough Concentration/Cycle | From start of treatment of the first subject until 15 months later assessed every 4 weeks. | Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID (bis in die, twice daily)) to assess any potential trends in trough concentration over time. |
| Average of All Trough Plasma Concentrations | From start of treatment of the first subject until 15 months later assessed every 4 weeks. | Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID). |
| Duration of Response According to the Independent Radiological Review for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact |
| Duration of Response According to the Investigator Assessment for the First Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks | Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact |
| Duration of Response According to the Investigator Assessment for the Second Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks | Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact |
| Time to Response According to the Independent Radiological Review for the First Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation was defined as the time from date of randomization to the earliest date that the response was first documented |
| Time to Response According to the Investigator Assessment for the First Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks | Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation was defined as the time from date of randomization to the earliest date that the response was first documented |
| Time to Response According to the Investigator Assessment for the Second Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks | Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation) was defined as the time from date of randomization to the earliest date that the response was first documented |
| Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks | Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst). |
| Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks | Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst). |
| Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | From randomization of the first subject until 15 months later, assessed every 8 weeks | The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated. |
Countries
France, Germany, Poland, Russia, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The start of enrollment was 14 June 2005 and the last day of enrollment was 12 September 2005.
Pre-assignment details
All 189 (97 Sorafenib/92 Interferon) randomized subjects were included in the intent to treat (ITT) population, and 187 (97 Sorafenib/90 Interferon) were included in the safety population according to the protocol, which defined eligibility for safety analyses by the prerequisite that a patient had received at least one dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg Subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (bid) (ie 12-hourly) orally until progression in (= first intervention period, 5.7 months \[median\] ) and 3 tablets of Sorafenib twice daily (ie 12-hourly) orally until the following progression (= second intervention period, 3.6 months \[median\]) on a continuous basis. | 97 |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg Interferon (IFN) a-2a was administered at a dose of 9 million international units(MIU) subcutaneously three times a week until progression (= first intervention period, 5.6 months \[median\]). Subjects initially started with a single dose of 3 MIU IFN and increased the dose as rapidly as possible to 9 MIU IFN three times a week within 1 or 2 weeks in first intervention period. After first progression, subjects received 2 tablets of Sorafenib (200 mg tablets) twice daily (BID) (ie 12-hourly) until the next progression (=second intervention period, 5.3 months \[median\]). | 92 |
| Total | 189 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (Period 1) | Adverse Event | 11 | 16 |
| First Intervention (Period 1) | investig. decision, not protocol driven | 0 | 1 |
| First Intervention (Period 1) | Lost to Follow-up | 0 | 2 |
| First Intervention (Period 1) | protocol driven decision point | 1 | 0 |
| First Intervention (Period 1) | Protocol Violation | 1 | 0 |
| First Intervention (Period 1) | reason not reported | 0 | 1 |
| First Intervention (Period 1) | study terminated by the sponsor | 3 | 1 |
| First Intervention (Period 1) | Withdrawal by Subject | 2 | 4 |
| Second Intervention (Period 2) | Adverse Event | 0 | 9 |
| Second Intervention (Period 2) | Lost to Follow-up | 1 | 0 |
| Second Intervention (Period 2) | non compliant with study medication | 1 | 1 |
| Second Intervention (Period 2) | Protocol Violation | 1 | 0 |
| Second Intervention (Period 2) | reason not reported | 1 | 0 |
| Second Intervention (Period 2) | study terminated by the sponsor | 2 | 9 |
| Second Intervention (Period 2) | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Total |
|---|---|---|---|
| Age, Continuous | 62 years | 62.5 years | 62 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 56 participants | 49 participants | 105 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 41 participants | 43 participants | 84 participants |
| Motzer risk factors high | 1 participants | 0 participants | 1 participants |
| Motzer risk factors intermediate | 44 participants | 44 participants | 88 participants |
| Motzer risk factors low | 52 participants | 47 participants | 99 participants |
| Motzer risk factors missing | 0 participants | 1 participants | 1 participants |
| Race Asian | 0 participants | 1 participants | 1 participants |
| Race Missing | 29 participants | 16 participants | 45 participants |
| Race White | 68 participants | 75 participants | 143 participants |
| Renal Cell Carcinoma (RCC) subtype clear cell | 85 participants | 81 participants | 166 participants |
| Renal Cell Carcinoma (RCC) subtype other variant | 12 participants | 11 participants | 23 participants |
| Sex: Female, Male Female | 32 Participants | 40 Participants | 72 Participants |
| Sex: Female, Male Male | 65 Participants | 52 Participants | 117 Participants |
| Time since first progression | 0.2 years | 0.2 years | 0.2 years |
| Time since initial diagnosis | 0.9 years | 1 years | 1 years |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 93 / 97 | 84 / 90 | 40 / 49 | 55 / 61 |
| serious Total, serious adverse events | 47 / 97 | 36 / 90 | 14 / 49 | 30 / 61 |
Outcome results
Primary
Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period | 5.7 months |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Progression-free Survival (PFS) Based on Independent Radiological Review for the First Intervention Period | 5.6 months |
Comparison: The study was planned to show a 80% improvement in PFS for the group treated with Sorafenib compared to the group treated with Interferon, with a 80% power and a 2-sided type I error of 5%p-value: 0.595% CI: [0.61, 1.27]Log Rank
Secondary
Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period
Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst).
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
Population: At the time of the analysis, only 95 subjects in Sorafenib 400 mg bid group and 89 in Interferon group were documented by study investigators due to various reasons (drop-out of patients by AEs, death etc.)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 0= Fully active without restriction | 20 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 1= Restricted in physically strenuous activity | 48 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 2= Ambulatory, capable of all selfcare | 20 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 3= Capable of limited selfcare | 5 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 4= Completely disabled | 1 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 5= Dead | 1 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 4= Completely disabled | 2 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 0= Fully active without restriction | 19 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 3= Capable of limited selfcare | 5 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 1= Restricted in physically strenuous activity | 42 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 5= Dead | 0 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the First Intervention Period | 2= Ambulatory, capable of all selfcare | 21 participants |
Secondary
Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period
Eastern Cooperative Oncology Group (ECOG) Performance Status is a scale that measures how cancer affects the daily life of a patient on an ordinal scale from grade 0 (best) to grade 5 (worst).
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
Population: At the time of the analysis, only 45 subjects in Sorafenib 400/600 mg bid group and 58 in Interferon/Sorafenib 400 mg bid group were documented by study investigators due to various reasons (drop-out of patients by AEs, death etc.)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 0= Fully active without restriction | 5 participant s |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 2= Ambulatory, capable of all selfcare | 10 participant s |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 5= Dead | 0 participant s |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 3= Capable of limited selfcare | 4 participant s |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 1= Restricted in physically strenuous activity | 25 participant s |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 4= Completely disabled | 1 participant s |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 5= Dead | 0 participant s |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 4= Completely disabled | 1 participant s |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 0= Fully active without restriction | 16 participant s |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 1= Restricted in physically strenuous activity | 26 participant s |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 2= Ambulatory, capable of all selfcare | 10 participant s |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Eastern Co-operative Oncology Group (ECOG) Status at the End of the Second Intervention Period | 3= Capable of limited selfcare | 5 participant s |
Secondary
Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period
The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions: I have been short in breath and I have been coughing; its score ranges from 0 to 8.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period | 6.4 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) After Intervention for the First Intervention Period | 5.1 scores on a scale |
Comparison: The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline) and using the baseline respiratory score as covariate.p-value: 0.022Mixed Models Analysis
Secondary
Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period
The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns. The respiratory domain of the FKSI comprises 2 questions: I have been short in breath and I have been coughing; its score ranges from 0 to 8.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period | 5.7 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Quality of Life by Use of the Respiratory Domain of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period | 6.4 scores on a scale |
Secondary
Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period
The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period | 40.5 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the First Intervention Period | 34.6 scores on a scale |
Comparison: The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline) and using the baseline respiratory score as covariate.p-value: 0.015Mixed Models Analysis
Secondary
Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period
The FKSI questionnaire comprises 15 questions dispatched within 4 domains (respiratory, pain, general symptoms and overall Quality of Life (QoL)) plus 2 individual items. Each question was answered on a five point scale from 0 (not at all) to 4 (very much) indicating the severity of symptoms. The total score range was from 0 to 60 with higher scores indicating subjects reported fewer kidney cancer related symptoms and concerns.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period | 34.6 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Quality of Life by Use of Total Score of the Functional Assessment of Cancer Therapy-Kidney Symptom Index (FKSI) for the Second Intervention Period | 42.3 scores on a scale |
Secondary
Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period
The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period | 104 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the First Intervention Period | 93 scores on a scale |
Comparison: The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).p-value: 0.073Mixed Models Analysis
Secondary
Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period
The FACT-BRM comprises 40 questions within 6 domains (physical well being, social/family well being, emotional well being, additional concern: physical, and additional concern: emotional). Each question was answered on a five point scale from 0 (not at all) to 4 (very much). The total score range is from 0 to 160 with higher scores indicating better QoL.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period | 89.7 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Quality of Life (QoL) by Use of Functional Assessment of Cancer Therapy-Biologic-response Modifiers (FACT-BRM) for the Second Intervention Period | 108.4 scores on a scale |
Secondary
Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | 82 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | 66 scores on a scale |
Comparison: The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).p-value: 0.001Mixed Models Analysis
Secondary
Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | 86.5 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Treatment Tolerability (Convenience) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | 82.5 scores on a scale |
Secondary
Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | 52 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | 42 scores on a scale |
Comparison: The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).p-value: 0.067Mixed Models Analysis
Secondary
Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | 56.9 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Treatment Tolerability (Effectiveness) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | 40.3 scores on a scale |
Secondary
Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | 60 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | 46 scores on a scale |
Comparison: The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).p-value: 0.019Mixed Models Analysis
Secondary
Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | 39.9 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Treatment Tolerability (Global Satisfaction) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | 35.4 scores on a scale |
Secondary
Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | 63 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the First Intervention Period | 46 scores on a scale |
Comparison: The least square (LS) means have been adjusted according to the stratification factors (geographical region, Motzer score at baseline).p-value: 0.005Mixed Models Analysis
Secondary
Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period
The TSQM comprises 14 questions dispatched within 4 domains (effectiveness, side effects, convenience, and global satisfaction). Each question was answered on either a 5-point or 7-point scale. Each domain score can vary from 0 to 100 with higher scores indicating subject reported higher effectiveness of treatment, less bothered by side-effects, more convenient use of medication and overall greater satisfaction with the treatment. No total score is calculated.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
Population: The number of analyzed patients regarding quality of life parameters varied considerably due to missing questionnaires which had not been filled in by patients or invalidity of these questionnaires according to the protocol.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | 61.3 scores on a scale |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Analysis of the Treatment Tolerability (Side Effects) by Use of Treatment Satisfaction Questionnaire for Medication (TSQM) for the Second Intervention Period | 57.6 scores on a scale |
Secondary
Average of All Trough Plasma Concentrations
Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID).
Time frame: From start of treatment of the first subject until 15 months later assessed every 4 weeks.
Population: Patients who started on Sorafenib, not Interferon, and had been at the same dose (400 mg or 600 mg BID) for at least 10 days were considered valid for the analysis. Concentrations collected between 10-14 hours from the last dose were included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Average of All Trough Plasma Concentrations | 93.9 100*mg/L |
Secondary
Disease Control (DC) According to Independent Central Review for the First Intervention Period
Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Disease Control (DC) According to Independent Central Review for the First Intervention Period | disease control (CR or PR or SD) | 77 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Disease Control (DC) According to Independent Central Review for the First Intervention Period | no disease control | 10 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Disease Control (DC) According to Independent Central Review for the First Intervention Period | Unknown | 10 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Disease Control (DC) According to Independent Central Review for the First Intervention Period | disease control (CR or PR or SD) | 59 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Disease Control (DC) According to Independent Central Review for the First Intervention Period | no disease control | 24 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Disease Control (DC) According to Independent Central Review for the First Intervention Period | Unknown | 9 participants |
p-value: 0.006Cochran-Mantel-Haenszel
Secondary
Disease Control (DC) According to the Investigator Assessment for the First Intervention Period
Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes.
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Disease Control (DC) According to the Investigator Assessment for the First Intervention Period | disease control (CR or PR or SD) | 83 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Disease Control (DC) According to the Investigator Assessment for the First Intervention Period | no disease control | 7 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Disease Control (DC) According to the Investigator Assessment for the First Intervention Period | Unknown | 7 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Disease Control (DC) According to the Investigator Assessment for the First Intervention Period | disease control (CR or PR or SD) | 62 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Disease Control (DC) According to the Investigator Assessment for the First Intervention Period | no disease control | 24 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Disease Control (DC) According to the Investigator Assessment for the First Intervention Period | Unknown | 6 participants |
p-value: 0.0004Cochran-Mantel-Haenszel
Secondary
Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period
Disease Control (DC) was defined as the total number of subjects whose best response was not Progressive Disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (= total number of Complete Response (CR) + total number of Partial Response (PR) + total number of Stable Disease (SD); CR, PR, or SD had to be maintained for at least 28 days from the first demonstration of that rating). CR: disappearance of tumor lesions (TL); PR: a decrease of at least 30% in the sum of TL sizes; SD: steady state of disease; PD: an increase of at least 20% in the sum of TL sizes.
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period | Unknown | 8 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period | disease control (CR or PR or SD) | 25 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period | no disease control | 16 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period | no disease control | 6 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period | Unknown | 6 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Disease Control (DC) According to the Investigator Assessment for the Second Intervention Period | disease control (CR or PR or SD) | 49 participants |
Secondary
Duration of Response According to the Independent Radiological Review for the First Intervention Period
Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Duration of Response According to the Independent Radiological Review for the First Intervention Period | 7.5 months |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Duration of Response According to the Independent Radiological Review for the First Intervention Period | 7.7 months |
Secondary
Duration of Response According to the Investigator Assessment for the First Intervention Period
Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Duration of Response According to the Investigator Assessment for the First Intervention Period | 4.4 months |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Duration of Response According to the Investigator Assessment for the First Intervention Period | 9.2 months |
Secondary
Duration of Response According to the Investigator Assessment for the Second Intervention Period
Duration of Response was defined as the time from date of first response (Complete Response (CR) or Partial Response (PR)) to the date when Progressive Disease (PD) is first documented or to the date of death, whichever occurs first. Subjects still having CR or PR at the time of analysis were censored at their last date of last contact
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Duration of Response According to the Investigator Assessment for the Second Intervention Period | 5.5 months |
Secondary
Overall Survival (OS)
Overall Survival was defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Overall Survival (OS) | 14.8 months |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Overall Survival (OS) | 26.9 months |
p-value: 0.014Log Rank
Secondary
Progression Free Survival According to the Investigator Assessment (Second Intervention Period)
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Progression Free Survival According to the Investigator Assessment (Second Intervention Period) | 4.5 months |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Progression Free Survival According to the Investigator Assessment (Second Intervention Period) | 5.5 months |
Secondary
Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period
Progression-free Survival (PFS) was defined as the time from date of randomization to disease progression (radiological or clinical or death due to any cause, whichever occurs first). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period | 5.6 months |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Progression-free Survival (PFS) Based on Investigator Assessment for the First Intervention Period | 7.0 months |
Comparison: The study was planned to show a 80% improvement in PFS for the group treated with Sorafenib compared to the group treated with Interferon, with a 80% power and a 2-sided type I error of 5%p-value: 0.46995% CI: [0.628, 1.239]Log Rank
Secondary
Slope - Change in Trough Concentration/Cycle
Plasma samples were collected prior to dosing every 4 weeks after the patient reached steady-state (at least 10 days at 400 mg BID (bis in die, twice daily)) to assess any potential trends in trough concentration over time.
Time frame: From start of treatment of the first subject until 15 months later assessed every 4 weeks.
Population: Patients who started on Sorafenib, not Interferon, and had been at the same dose (400 mg) for at least 10 days were considered valid for the analysis. Concentrations collected between 10-14 hours from the last dose were included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Slope - Change in Trough Concentration/Cycle | -8.3 100*(mg/L/cycle) |
Secondary
Time to Response According to the Independent Radiological Review for the First Intervention Period
Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation was defined as the time from date of randomization to the earliest date that the response was first documented
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Time to Response According to the Independent Radiological Review for the First Intervention Period | 1.8 months |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Time to Response According to the Independent Radiological Review for the First Intervention Period | 5.4 months |
Secondary
Time to Response According to the Investigator Assessment for the First Intervention Period
Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation was defined as the time from date of randomization to the earliest date that the response was first documented
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Time to Response According to the Investigator Assessment for the First Intervention Period | 3.5 months |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Time to Response According to the Investigator Assessment for the First Intervention Period | 5.4 months |
Secondary
Time to Response According to the Investigator Assessment for the Second Intervention Period
Time to Response (TTR) for subjects who achieved a response (Complete Response (CR) or Partial Response (PR) with confirmation) was defined as the time from date of randomization to the earliest date that the response was first documented
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Time to Response According to the Investigator Assessment for the Second Intervention Period | 1.7 months |
Secondary
Tumor Response According to the Independent Radiological Review for the First Intervention Period
Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes.
Time frame: From randomization of the first subject until 15 months later, assessed every 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Not Evaluated | 10 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Complete Response (CR) | 0 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Partial Response (PR) | 5 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Stable Disease (SD) | 72 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Progressive Disease (PD) | 10 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Progressive Disease (PD) | 24 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Stable Disease (SD) | 51 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Complete Response (CR) | 1 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Not Evaluated | 9 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Independent Radiological Review for the First Intervention Period | Partial Response (PR) | 7 participants |
Secondary
Tumor Response According to the Investigator Assessment for the First Intervention Period
Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Partial Response (PR) | 21 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Progressive Disease (PD) | 7 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Stable Disease (SD) | 62 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Not Evaluated | 7 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Complete Response (CR) | 0 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Not Evaluated | 6 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Complete Response (CR) | 1 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Partial Response (PR) | 13 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Stable Disease (SD) | 48 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the First Intervention Period | Progressive Disease (PD) | 24 participants |
Secondary
Tumor Response According to the Investigator Assessment for the Second Intervention Period
Tumor Response (= Best Overall Response) of a subject was defined as the best tumor response (confirmed Complete Response (CR), confirmed Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)) observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, SD was defined as steady state of disease, PD was defined as an increase of at least 20% in the sum of tumor lesions sizes
Time frame: From randomization of the first subject until 3 years and 9 months later, assessed every 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Partial Response (PR) | 0 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Progressive Disease (PD) | 16 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Stable Disease (SD) | 25 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Not Evaluated | 8 participants |
| First Sorafenib (Nexavar, BAY43-9006) 400 mg Then 600 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Complete Response (CR) | 0 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Not Evaluated | 6 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Complete Response (CR) | 1 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Partial Response (PR) | 11 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Stable Disease (SD) | 37 participants |
| First Interferon Then Sorafenib (Nexavar, BAY43-9006) 400 mg | Tumor Response According to the Investigator Assessment for the Second Intervention Period | Progressive Disease (PD) | 6 participants |