Carcinoma, Renal Cell
Conditions
Keywords
Kidney cancer,, Sorafenib,, Dose escalation,, No previous treatment
Brief summary
Sorafenib is a new drug, which is approved under the brand name Nexavar for the treatment of advanced kidney cancer. It is also currently being tested in various other cancers. Sorafenib works by stopping the development of new cancer cells and new blood vessels. By stopping the growth of new blood vessels around a tumor, it is believed that sorafenib prevents the growth of kidney cancer tumors. This is an open-label study which means that the patient, the doctor and Bayer Healthcare will know what tablets the patient is taking. All patients in this study will receive sorafenib tablets. Sorafenib is taken orally as a tablet (two tablets are taken twice a day). Treatment with sorafenib will continue until the patient's tumor grows larger or spreads further or if the patient has intolerable side effects. The dose of sorafenib that the patient will receive in the study will increase at certain points during the patient's treatment, as long as the patient is not experiencing side effects and the patient's tumor has not grown.
Detailed description
Issues on Outcome Measure Safety and tolerability will be addressed in the Adverse Events section.
Interventions
DRUGSorafenib (Nexavar, BAY43-9006)
The initial dose of sorafenib will be 400 mg bid administered orally, on a continuous basis. A treatment cycle is considered to be 28 days. Intrapatient dose escalation will occur according to the following schedule, providing no grade 3 or 4 toxicities are observed (except for alopecia, nausea and vomiting); Day 1-28 400 mg bid, Day 29-56 600 mg bid, Day 57 onwards 800 mg bid. Subjects will continue on treatment until progression, unacceptable toxicity, subject withdraws consent or the decision is taken to stop the study following the analysis of response rates.
Sponsors
Bayer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years. * Metastatic clear cell RCC (renal cell carcinoma) * Subjects with at least one uni-dimensional measurable lesion. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Memorial Sloan Kettering Cancer Center (MSKCC) good or intermediate category * Life expectancy of at least 12 weeks. * Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to treatment * Signed informed consent must be obtained prior to any study specific procedures. * Subjects must have received no prior systemic anticancer therapy for the treatment of their renal cell carcinoma * Prior total nephrectomy
Exclusion criteria
* History of cardiac disease * History of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C * Active clinically serious infections (\> grade 2 National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] version 3.0) * Symptomatic metastatic brain or meningeal tumors unless the subject is \> 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. * Subjects with evidence or history of bleeding diathesis * Deep vein thrombosis and/or pulmonary embolus within 12 months of the start of treatment. * Delayed healing of wounds, ulcers or bone fractures * Subjects with pre-existing thyroid abnormality whose thyroid function cannot be maintained within the normal range by medication * Subjects undergoing renal dialysis * Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to 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 and three months after the completion of trial. * Prior adjuvant sorafenib is excluded. * Radiotherapy during study or within 3 weeks of start of study drug * Major surgery within 4 weeks of start of study * Investigational drug therapy outside of this trial during or within 4 weeks of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response - ITT (Intent to Treat) Population | Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. | Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions. |
| Best Response - mITT (Modified Intent-to-treat) Population | Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. | Best Response (Response Rate) of a subject was defined as the proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor and PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) | Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose. | AUC(0-12),ss was defined as an area under the plasma concentration versus time curve from time zero to 12 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib. |
| Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax) | Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose. | Cmax was defined as a maximum plasma concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib. |
| Progression-free Survival (PFS) | Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. | Progression-free survival (PFS) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment or death due to any cause whichever occurred first. For patients who had not recurred or died at the time of analysis, PFS was censored at their last date of evaluable scan. |
| Time to Progression (TTP) | Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. | Time to progression (TTP) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment whichever occurred first. For patients who had not progressed at the time of analysis or died before progression, TTP was censored at their last date of evaluable scan. |
| Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax) | Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose. | Tmax was defined as a time to maximum concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib. |
| Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) | Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8 and 10 hours post-dose. | AUC(0-10),ss was defined as an area under the plasma concentration versus time curve from time zero to 10 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response - mITT Population | Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. | Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions. |
| Disease Control - mITT Population | Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months. | Disease Control (DC) of a subject was defined as the proportion of patients with confirmed Complete Response (CR), Partial Response (PR) or Stable Disease (SD) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, and SD was defined as steady state of disease. |
Countries
France, Germany, Italy, Poland, United Kingdom
Participant flow
Recruitment details
Subjects were enrolled from 04 Feb to 05 Nov 2008 at 19 centers in 5 countries (Germany, France, United Kingdom, Italy and Poland).
Pre-assignment details
Of the 89 subjects enrolled, 83 were treated with the study drug. Safety population = 83 subjects who took at least one dose of study drug and had any data after baseline. Intent to treat population = 67 subjects treated with the study drug who had at least one efficacy evaluation after baseline.
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) Intrapatient dose escalation of sorafenib from 400 mg orally twice daily (bid) for the first cycle, 600 mg bid for the second cycle and 800 mg bid until disease progression, unacceptable toxicity or withdrawal of consent. Dose reductions due to toxicities were allowed. | 83 |
| Total | 83 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 23 |
| Overall Study | ongoing, still treated with study med. | 25 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Sorafenib (Nexavar, BAY43-9006) |
|---|---|
| Age, Continuous | 61 years |
| ECOG (Eastern Cooperative Oncology Group) Performance Status 0 | 49 participants |
| ECOG (Eastern Cooperative Oncology Group) Performance Status 1 | 34 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 54 Participants |
| Stage at study entry Stage III | 1 participants |
| Stage at study entry Stage IV | 82 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 80 / 83 |
| serious Total, serious adverse events | 45 / 83 |
Outcome results
Primary
Best Response - mITT (Modified Intent-to-treat) Population
Best Response (Response Rate) of a subject was defined as the proportion of patients with confirmed Complete Response (CR) or Partial Response (PR) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor and PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes.
Time frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Population: The population for the analysis of primary efficacy variable was the modified intent-to-treat (mITT) population defined as the patients treated for at least 6 months with 4 months at their highest tolerated dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Best Response - mITT (Modified Intent-to-treat) Population | 8 Participants |
Primary
Tumor Response - ITT (Intent to Treat) Population
Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions.
Time frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Population: The population for the efficacy analysis was the intent-to-treat (ITT) population defined as all patients who received at least one dose of study medication with at least one valid tumor assessment post-baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Tumor Response - ITT (Intent to Treat) Population | Complete Response (CR) | 0 participants |
| Sorafenib (Nexavar, BAY43-9006) | Tumor Response - ITT (Intent to Treat) Population | Partial Response (PR) | 12 participants |
| Sorafenib (Nexavar, BAY43-9006) | Tumor Response - ITT (Intent to Treat) Population | Stable Disease (SD) | 46 participants |
| Sorafenib (Nexavar, BAY43-9006) | Tumor Response - ITT (Intent to Treat) Population | Progressive Disease (PD) | 9 participants |
Secondary
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss)
AUC(0-10),ss was defined as an area under the plasma concentration versus time curve from time zero to 10 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Time frame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8 and 10 hours post-dose.
Population: PK Analysis Population. 40 participants in the 400 mg bid group that had an AUC(0-10)ss calculated; 30 participants in the 600 mg bid group that had an AUC(0-10)ss calculated; 26 participants and 27 participants in the 800 mg bid group that had an AUC(0-10)ss calculated, for sorafenib and M2 parameter respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) | Sorafenib (N=40, 30, 26) | 50.0 mg*h/L | Geometric Coefficient of Variation 39.2 |
| Sorafenib (Nexavar, BAY43-9006) | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) | M2 (BAY67-3472) (N=40, 30, 27) | 8.80 mg*h/L | Geometric Coefficient of Variation 74.3 |
| Sorafenib (Nexavar, BAY43-9006)_600 mg | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) | Sorafenib (N=40, 30, 26) | 51.2 mg*h/L | Geometric Coefficient of Variation 43.7 |
| Sorafenib (Nexavar, BAY43-9006)_600 mg | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) | M2 (BAY67-3472) (N=40, 30, 27) | 10.4 mg*h/L | Geometric Coefficient of Variation 82.1 |
| Sorafenib (Nexavar, BAY43-9006)_800 mg | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) | Sorafenib (N=40, 30, 26) | 43.8 mg*h/L | Geometric Coefficient of Variation 47.8 |
| Sorafenib (Nexavar, BAY43-9006)_800 mg | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 10 Hours Postdose (AUC(0-10),ss) | M2 (BAY67-3472) (N=40, 30, 27) | 8.23 mg*h/L | Geometric Coefficient of Variation 87.2 |
Secondary
Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss)
AUC(0-12),ss was defined as an area under the plasma concentration versus time curve from time zero to 12 hours post-dose. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Time frame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
Population: PK Analysis Population. 32 participants in the 400 mg bid group that had an AUC(0-12)ss calculated; 23 participants in the 600 mg bid group that had an AUC(0-12)ss calculated; 19 participants and 20 participants in the 800 mg bid group that had an AUC(0-12)ss calculated, for sorafenib and M2 parameter respectively.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) | Sorafenib (N=32, 23, 19) | 57.2 mg*h/L | Geometric Coefficient of Variation 39.1 |
| Sorafenib (Nexavar, BAY43-9006) | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) | M2 (BAY67-3472) (N=32, 23, 20) | 9.58 mg*h/L | Geometric Coefficient of Variation 78.2 |
| Sorafenib (Nexavar, BAY43-9006)_600 mg | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) | Sorafenib (N=32, 23, 19) | 57.6 mg*h/L | Geometric Coefficient of Variation 46.1 |
| Sorafenib (Nexavar, BAY43-9006)_600 mg | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) | M2 (BAY67-3472) (N=32, 23, 20) | 11.2 mg*h/L | Geometric Coefficient of Variation 75.9 |
| Sorafenib (Nexavar, BAY43-9006)_800 mg | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) | Sorafenib (N=32, 23, 19) | 47.0 mg*h/L | Geometric Coefficient of Variation 51.9 |
| Sorafenib (Nexavar, BAY43-9006)_800 mg | Pharmacokinetics (PK) Analysis - Area Under the Drug Concentration-time Curve From Time Zero to 12 Hours Postdose (AUC(0-12),ss) | M2 (BAY67-3472) (N=32, 23, 20) | 8.41 mg*h/L | Geometric Coefficient of Variation 94.6 |
Secondary
Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax)
Cmax was defined as a maximum plasma concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Time frame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
Population: PK Analysis Population. 40 participants in the 400 mg bid group that had Cmax calculated; 31 participants in the 600 mg bid group that had Cmax calculated; 28 participants in the 800 mg bid group that had Cmax calculated.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax) | Sorafenib | 7.53 mg/L | Geometric Coefficient of Variation 38 |
| Sorafenib (Nexavar, BAY43-9006) | Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax) | M2 (BAY67-3472) | 1.31 mg/L | Geometric Coefficient of Variation 80.8 |
| Sorafenib (Nexavar, BAY43-9006)_600 mg | Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax) | Sorafenib | 7.62 mg/L | Geometric Coefficient of Variation 39.3 |
| Sorafenib (Nexavar, BAY43-9006)_600 mg | Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax) | M2 (BAY67-3472) | 1.51 mg/L | Geometric Coefficient of Variation 81.4 |
| Sorafenib (Nexavar, BAY43-9006)_800 mg | Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax) | Sorafenib | 6.64 mg/L | Geometric Coefficient of Variation 42.1 |
| Sorafenib (Nexavar, BAY43-9006)_800 mg | Pharmacokinetics (PK) Analysis - Maximum Observed Concentration in Plasma (Cmax) | M2 (BAY67-3472) | 1.30 mg/L | Geometric Coefficient of Variation 88.5 |
Secondary
Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax)
Tmax was defined as a time to maximum concentration at steady-state. Parameter was calculated for sorafenib and M2, an active metabolite of sorafenib.
Time frame: Blood samples were collected at screening (blank) and on day 28 of the first cycle completed at each dose level. Samples were drawn at the following time points in relation to morning dose of sorafenib: pre-dose, 2, 4, 6, 8, 10 and 12 hours post-dose.
Population: PK Analysis Population. 40 participants in the 400 mg bid group that had Tmax calculated; 31 participants in the 600 mg bid group that had Tmax calculated; 28 participants in the 800 mg bid group that had Tmax calculated.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax) | Sorafenib | 2 hours |
| Sorafenib (Nexavar, BAY43-9006) | Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax) | M2 (BAY67-3472) | 2 hours |
| Sorafenib (Nexavar, BAY43-9006)_600 mg | Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax) | Sorafenib | 2 hours |
| Sorafenib (Nexavar, BAY43-9006)_600 mg | Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax) | M2 (BAY67-3472) | 2 hours |
| Sorafenib (Nexavar, BAY43-9006)_800 mg | Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax) | Sorafenib | 2 hours |
| Sorafenib (Nexavar, BAY43-9006)_800 mg | Pharmacokinetics (PK) Analysis - Time to Maximum Concentration (Tmax) | M2 (BAY67-3472) | 1 hours |
Secondary
Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment or death due to any cause whichever occurred first. For patients who had not recurred or died at the time of analysis, PFS was censored at their last date of evaluable scan.
Time frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Population: Intent-to-treat (ITT).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Progression-free Survival (PFS) | 7.4 months |
Secondary
Time to Progression (TTP)
Time to progression (TTP) was defined as the time from start of study medication to the first documented disease progression per RECIST (by independent radiological assessment) or clinical progression as per investigator assessment whichever occurred first. For patients who had not progressed at the time of analysis or died before progression, TTP was censored at their last date of evaluable scan.
Time frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Population: Intent-to treat (ITT).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Time to Progression (TTP) | 7.4 months |
Other Pre-specified
Disease Control - mITT Population
Disease Control (DC) of a subject was defined as the proportion of patients with confirmed Complete Response (CR), Partial Response (PR) or Stable Disease (SD) as their best response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed CR was defined as disappearance of tumor, PR was defined as a decrease of at least 30% in the sum of tumor lesion sizes, and SD was defined as steady state of disease.
Time frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Population: The population for the analysis of primary efficacy variable was the modified intent-to-treat (mITT) population defined as the patients treated for at least 6 months with 4 months at their highest tolerated dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Disease Control - mITT Population | 18 Participants |
Other Pre-specified
Tumor Response - mITT Population
Tumor Response of a subject was defined as the best tumor response observed (by independent central assessment) during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST version 1.0) criteria. Confirmed Complete Response (CR) was defined as disappearance of tumor, Partial Response (PR) was defined as a decrease of at least 30% in the sum of target lesions, Stable Disease (SD) was defined as steady state of disease, and Progressive Disease (PD) was defined as at least a 20% increase in the sum of measured lesions or appearance of new lesions.
Time frame: Radiological assessments were performed every 8 weeks (2 cycles) from start of the treatment. After completion of 6 cycles of treatment at the highest tolerated dose level, assessments were performed every 12 weeks for up to 34 months.
Population: The population for the analysis of primary efficacy variable was the modified intent-to-treat (mITT) population defined as the patients treated for at least 6 months with 4 months at their highest tolerated dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Tumor Response - mITT Population | Complete response (CR) | 0 Participants |
| Sorafenib (Nexavar, BAY43-9006) | Tumor Response - mITT Population | Partial response (PR) | 8 Participants |
| Sorafenib (Nexavar, BAY43-9006) | Tumor Response - mITT Population | Stable disease (SD) | 10 Participants |
| Sorafenib (Nexavar, BAY43-9006) | Tumor Response - mITT Population | Progressive disease (PD) | 0 Participants |