A Study to Assess Sorafenib Alone and in Combination With Low-Dose Interferon Following Unsuccessful Treatment With Sunitinib in Patients With Advanced Renal Cell Cancer.

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II, Randomized, Open-label, Multicenter, Study Evaluating the Efficacy of Sorafenib Alone and Sorafenib in Combination With Low Dose Interferon Alpha-2a as Second-line Treatment of Sunitinib Failure in Patients With Metastatic Renal Cell Carcinoma

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: Sorafenib (Nexavar, BAY43-9006)
* Drug: Sorafenib (Nexavar, BAY43-9006) + Interferon


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib (Nexavar, BAY43-9006)<br>Sorafenib 400 mg (two 200 mg tablets) twice daily (bid) per os (po), continuously. | Drug: Sorafenib (Nexavar, BAY43-9006)<br>* Sorafenib 400 mg (two 200 mg tablets) BID PO, continuously<br>|
| Experimental: Sorafenib (Nexavar, BAY43-9006) + Interferon<br>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. | Drug: Sorafenib (Nexavar, BAY43-9006) + Interferon<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From start of treatment of the first subject until 14 months later, assessed every 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From start of treatment of the first subject until 14 months later, assessed every 8 Weeks | 
| 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. | From start of treatment of the first subject until 14 months later, assessed every 8 Weeks | 
| 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. | From start of treatment of the first subject until 14 months later, assessed every 8 Weeks | 
| 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. | From start of treatment of the first subject until 14 months later, assessed every 8 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Cell Cancer, Interferon