Carcinoma, Renal Cell
Conditions
Keywords
Sorafenib, Nexavar, Metastatic RCC, Renal Cell Carcinoma, Unresectable RCC
Brief summary
Extension to study 11515 (NCT00661375) which was a multicenter study of sorafenib in patients with renal cell carcinoma (RCC).
Interventions
DRUGSorafenib (Nexavar, BAY43-9006)
Sorafenib 200 mg tablets (400 mg \[2 x 200 mg tablets\] twice daily \[bid\] or 400 mg once daily \[od\] or 400 mg every other day \[qod\]) administered orally
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients are classified into two groups as below at transition date from Study 11515 to this study. Population I: Patients who are willing to continue the study drug, for whom the investigator consider continuation of the study drug is appropriate, and who do not meet the criteria of removal from the study in Study 11515 at the end of Study 11515. Population II: Patients who have been monitored only for survival status at the end of Study 11515. Population 1 1. Patients who are willing to continue the study drug, 2. Patients for whom the investigator consider continuation of the study drug is appropriate 3. Patients who do not meet the criteria of removal from the study in Study 11515 at the end of Study 11515. 4. 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. Population 2 1\. 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.
Exclusion criteria
1. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results 2. Any condition that could jeopardize the safety of the patient or that affect his/her compliance in the study 3. Pregnant or breast-feeding patients. Both men and women enrolled in this trial must use adequate birth control.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From start of treatment of the first subject until 45 months later, assessed every 8 weeks | Time from initiation of treatment to disease progression (radiological or clinical, whichever earlier) or death (if death occurs before progression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Tumor Response | From start of treatment of the first subject until 45 months later, assessed every 8 weeks | Best tumor response, including Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter) according to the Response Evaluation Criteria in Solid Tumors (RECIST) |
| Overall Survival (OS) | From start of treatment of the first subject until 45 months later, assessed every 3 months | Time from initiation of treatment to death due to any cause. |
| Overall Response Duration | From start of treatment of the first subject until 45 months later, assessed every 8 weeks | Time from the date of first objective response (CR or PR, whichever is first recorded) to the date when progressive disease (PD, at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions) is first documented according to RECIST. |
| Time to Objective Response | From start of treatment of the first subject until 45 months later, assessed every 8 weeks | Time from initiation of treatment to the date when an objective response (CR or PR, whichever is first recorded) is first documented according to RECIST. |
| Overall Disease Control | From start of treatment of the first subject until 45 months later, assessed every 8 weeks | Subjects who have a best response rating of CR, PR or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started) per RECIST that is maintained for at least 28 days from the first demonstration of that rating. |
Countries
Japan
Participant flow
Recruitment details
This was an extension study of Study 11515 (NCT00661375), in which the first subject was enrolled on 10 Nov 2004. This extension study was started in December 2005, and the last subject completed the study on 11 Jul 2008. The study was conducted in 41 centers in Japan.
Pre-assignment details
95 subjects were enrolled in this extension study; 95 were valid for the safety analysis and 94 were valid for the intent-to treat (ITT) analysis. 92 subjects entered Follow-up period which started 30 days after last dose. 3 subjects did not enter the Follow-up period because they died within 30 days after last dose.
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) Sorafenib 200 mg tablets (400 mg \[2 x 200 mg tablets\] twice daily \[bid\] or 400 mg once daily \[od\] or 400 mg every other day \[qod\]) administered orally | 95 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Follow-up | Death | 40 |
| Follow-up | Lost to Follow-up | 1 |
| Follow-up | Protocol driven decision point | 37 |
| Follow-up | Switch to commercial drug | 10 |
| Follow-up | Withdrawal by Subject | 4 |
| Treatment Period | Adverse Event | 11 |
| Treatment Period | Death | 1 |
| Treatment Period | Disease progression, recurrence/relapse | 71 |
| Treatment Period | Protocol Violation | 1 |
| Treatment Period | Switch to commercial drug | 10 |
| Treatment Period | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Sorafenib (Nexavar, BAY43-9006) |
|---|---|
| Age Continuous | 62.0 years STANDARD_DEVIATION 10.5 |
| Age, Customized <65 years | 54 participants |
| Age, Customized >=65 years | 41 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 0 | 80 participants |
| Eastern Cooperative Oncology Group (ECOG) performance status 1 | 15 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 95 / 95 |
| serious Total, serious adverse events | 34 / 95 |
Outcome results
Primary
Progression Free Survival (PFS)
Time from initiation of treatment to disease progression (radiological or clinical, whichever earlier) or death (if death occurs before progression).
Time frame: From start of treatment of the first subject until 45 months later, assessed every 8 weeks
Population: Intention to treat (ITT) population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Progression Free Survival (PFS) | 386 days |
Secondary
Best Tumor Response
Best tumor response, including Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter) according to the Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: From start of treatment of the first subject until 45 months later, assessed every 8 weeks
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Best Tumor Response | Complete Response (CR) | 0 participants |
| Sorafenib (Nexavar, BAY43-9006) | Best Tumor Response | Partial Response (PR) | 25 participants |
| Sorafenib (Nexavar, BAY43-9006) | Best Tumor Response | Stable Disease (SD) | 64 participants |
| Sorafenib (Nexavar, BAY43-9006) | Best Tumor Response | Disease Progression (radiological or clinical) | 4 participants |
| Sorafenib (Nexavar, BAY43-9006) | Best Tumor Response | Not evaluated | 1 participants |
Secondary
Overall Disease Control
Subjects who have a best response rating of CR, PR or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started) per RECIST that is maintained for at least 28 days from the first demonstration of that rating.
Time frame: From start of treatment of the first subject until 45 months later, assessed every 8 weeks
Population: ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Overall Disease Control | 81 participants |
Secondary
Overall Response Duration
Time from the date of first objective response (CR or PR, whichever is first recorded) to the date when progressive disease (PD, at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions) is first documented according to RECIST.
Time frame: From start of treatment of the first subject until 45 months later, assessed every 8 weeks
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Overall Response Duration | 419 days |
Secondary
Overall Survival (OS)
Time from initiation of treatment to death due to any cause.
Time frame: From start of treatment of the first subject until 45 months later, assessed every 3 months
Population: ITT population. The median overall survival (OS) and the lower limit of 95% Confidence interval were not estimable because more than half (n=51) of the study population were censored. The number of participant who died is shown in Post-Hoc Outcome Measure: Number of Participants who Died.
Secondary
Time to Objective Response
Time from initiation of treatment to the date when an objective response (CR or PR, whichever is first recorded) is first documented according to RECIST.
Time frame: From start of treatment of the first subject until 45 months later, assessed every 8 weeks
Population: ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Time to Objective Response | 84 days |
Post Hoc
Number of Participants Who Died
Number of subjects who died due to any cause.
Time frame: From start of treatment of the first subject until 45 months later, assessed every 3 months
Population: Overall Survival is shown in Secondary Outcome Measure: Overall Survival.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sorafenib (Nexavar, BAY43-9006) | Number of Participants Who Died | 43 participants |