Carcinoma, Renal Cell
Conditions
Keywords
Renal Cell Cancer, Interferon
Brief summary
This study is to assess sorafenib as second treatment for patients that have previously received only sunitinib as first-line treatment for advanced renal cell cancer, and who either responded and then progressed with sunitinib or were intolerant to sunitinib. This study is to assess if combining the usual dose of sorafenib (200mg twice-daily) with low dose interferon (3 million international unit (MIU) five times a week) can treat kidney cancer more effectively than the current approved dose alone and if it is safe. In addition, for patients that respond to treatment with sorafenib alone or in combination with interferon before progressing, patients may receive sorafenib alone at an increased dose of 300mg twice-daily, provided that toxicities are acceptable and at the discretion of the investigator.
Interventions
DRUGSorafenib (Nexavar, BAY43-9006)
Sorafenib 400 mg (two 200 mg tablets) BID PO, continuously
DRUGSorafenib (Nexavar, BAY43-9006) + Interferon
Sorafenib 400 mg (two 200 mg tablets) BID PO, continuously. IFN alpha-2a 3MIU FIW s.c., from Monday to Friday (total weekly dose 15 MIU) s.c., to start one week after commencing sorafenib.
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
* Disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria following documented stable disease or better after at least 8 weeks of sunitinib as first-line treatment (or two cycles of 4 weeks on and 2 weeks off treatment) * And/or patients who have discontinued sunitinib treatment at any point due to toxicity * Study entry at least 2 weeks after treatment with sunitinib but up to a maximum of 8 weeks * Memorial Sloane Kettering Cancer Centre (MSKCC) prognostic score low or intermediate * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Patient must have histologically confirmed metastatic renal cell carcinoma with predominant clear cell histology (clear cell component more than 50%).
Exclusion criteria
* Patient should be excluded if they have unresolved chronic toxicity grade * \> 1 and related to prior therapy with sunitinib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From start of treatment of the first subject until 14 months later, assessed every 8 weeks | Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier, according to Response Evaluation Criteria in Solid Tumors \[RECIST\]) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | From start of treatment of the first subject until 14 months later, assessed every 8 Weeks | Response Rate was the best tumor response (confirmed Complete Response \[CR\], Partial Response \[PR\] or Stable Disease \[SD\]) observed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. |
| Time to Progression | From start of treatment of the first subject until 14 months later, assessed every 8 Weeks | Time to progression was the time from treatment start date to disease progression. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation. |
| Duration of Response | From start of treatment of the first subject until 14 months later, assessed every 8 Weeks | Duration of Response was 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. |
| Overall Survival | From start of treatment of the first subject until 14 months later, assessed every 8 Weeks | Overall Survival was the time from treatment start date to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact. |
Countries
Austria, France, Ireland, Italy, Poland, Spain, United Kingdom
Participant flow
Recruitment details
This study was conducted from 16 Apr 2008 to 26 Jun 2009 at 31 centers in 7 countries: France (11), Italy (6), Spain (5), Poland (4), Ireland (2), United Kingdom (2), and Austria (1). The planned enrollment was 120 subjects in the 2 treatment groups (60 subjects per group). The study was stopped early because of slow accrual.
Pre-assignment details
A total of 24 subjects were screened; 16 were enrolled and randomized; 10 (63%) to sorafenib alone and 6 (37%) to sorafenib + interferon. All 16 randomized subjects received at least 1 dose of study drug and were included in the safety analysis population.
Participants by arm
| Arm | Count |
|---|---|
| Sorafenib (Nexavar, BAY43-9006) Sorafenib 400 mg (two 200 mg tablets) twice daily (bid) per os (po), continuously. | 10 |
| Sorafenib (Nexavar, BAY43-9006) + Interferon Sorafenib 400 mg (two 200 mg tablets) twice daily (bid) per os (po), continuously plus Interferon (IFN) alpha-2a 3 millions of international unit (MIU) five times a week (FIW) subcutaneous (s.c.), from Monday to Friday (total weekly dose 15 MIU) s.c., to start one week after commencing sorafenib. | 6 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Disease progression/recurrence/relapse | 6 | 1 |
| Overall Study | Not compliant with study medication | 0 | 1 |
| Overall Study | Reason not reported | 1 | 0 |
| Overall Study | Study terminated by the sponsor | 2 | 0 |
| Overall Study | Switch to commercial drug | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Sorafenib (Nexavar, BAY43-9006) | Sorafenib (Nexavar, BAY43-9006) + Interferon | Total |
|---|---|---|---|
| Age, Continuous | 57 years | 60.5 years | 58.5 years |
| Memorial Sloane Kettering Cancer Center (MSKCC) score intermediate MSKCC score | 7 participants | 5 participants | 12 participants |
| Memorial Sloane Kettering Cancer Center (MSKCC) score low MSKCC score | 3 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 10 | 5 / 6 |
| serious Total, serious adverse events | 5 / 10 | 3 / 6 |
Outcome results
Primary
Progression-Free Survival
Progression-free Survival (PFS) was the time from the first dose of combination therapy to disease progression (radiological or clinical, whichever is earlier, according to Response Evaluation Criteria in Solid Tumors \[RECIST\]) or death (if death occurs before progression is documented). PFS for subjects without tumor progression or death at the time of analysis were censored at the date of last tumor evaluation.
Time frame: From start of treatment of the first subject until 14 months later, assessed every 8 weeks
Population: Efficacy analysis was not performed due to low accrual. For details, please see Limitation and Caveats.
Secondary
Duration of Response
Duration of Response was 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 start of treatment of the first subject until 14 months later, assessed every 8 Weeks
Population: Efficacy analysis was not performed due to low accrual. For details, please see Limitation and Caveats.
Secondary
Overall Survival
Overall Survival was the time from treatment start date 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 start of treatment of the first subject until 14 months later, assessed every 8 Weeks
Population: Efficacy analysis was not performed due to low accrual. For details, please see Limitation and Caveats.
Secondary
Response Rate
Response Rate was the best tumor response (confirmed Complete Response \[CR\], Partial Response \[PR\] or Stable Disease \[SD\]) observed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Time frame: From start of treatment of the first subject until 14 months later, assessed every 8 Weeks
Population: Efficacy analysis was not performed due to low accrual. For details, please see Limitation and Caveats.
Secondary
Time to Progression
Time to progression was the time from treatment start date to disease progression. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation.
Time frame: From start of treatment of the first subject until 14 months later, assessed every 8 Weeks
Population: Efficacy analysis was not performed due to low accrual. For details, please see Limitation and Caveats.