Sorafenib and Interferon Alfa in Treating Patients With Locally Advanced or Metastatic Kidney Cancer

Study Overview
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Brief Summary
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Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth or by blocking blood flow to the tumor. Interferon alfa may interfere with the growth of tumor cells and slow the growth of kidney cancer. Sorafenib may help interferon alfa kill more tumor cells by making tumor cells more sensitive to the drug. Giving sorafenib together with interferon alfa may kill more tumor cells. This phase II trial is studying how well giving sorafenib with interferon alfa works in treating patients with locally advanced or metastatic kidney cancer.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the feasibility and tolerability of sorafenib and interferon alfa in patients with locally advanced or metastatic renal cell carcinoma. II. Determine the response rate (complete response and partial response) in patients treated with this regimen. SECONDARY OBJECTIVES: I. Determine the progression-free survival and response duration of patients treated with this regimen. II. Correlate changes in laboratory parameters with response in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive oral sorafenib twice daily and interferon alfa subcutaneously three times a week for 8 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease are followed every 3 months for 2 years, every 6 months for 2 years, and then annually for 1 year or until disease progression. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 10 months.

Official Title
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A Phase 2 Study Of BAY 43-9006 In Combination With Interferon Alfa-2b In Metastatic Renal Cell Cancer

Conditions
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Clear Cell Renal Cell Carcinoma, Papillary Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage III Renal Cell Cancer, Stage IV Renal Cell Cancer

Intervention / Treatment
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* Drug: sorafenib tosylate
* Biological: recombinant interferon alfa
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed renal cell carcinoma Locally advanced or metastatic disease All histologic subtypes allowed Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan No known brain metastases or leptomeningeal disease Performance status - ECOG 0-2 WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No bleeding diathesis Bilirubin normal AST and ALT ≤ 2.5 times upper limit of normal (ULN) Creatinine ≤ 1.5 times ULN Creatinine clearance ≥ 60 mL/min No uncontrolled hypertension No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No history of sensitivity to E. coli-derived products No history of severe depression No active infection requiring antibiotics No seizure disorder requiring antiepileptic medication No medical condition likely to require systemic corticosteroids No autoimmune disorder that could result in life-threatening complications No other uncontrolled illness No psychiatric illness or social situation that would preclude study compliance No more than 1 prior biologic response modifier regimen At least 4 weeks since prior biologic response modifiers No prior interferon alfa No prior chemotherapy At least 4 weeks since prior radiotherapy to non-index lesions Prior radiotherapy to index lesion allowed provided irradiated lesion progressed ≥ 20% in diameter At least 2 weeks since prior major surgery No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent therapeutic anticoagulation therapy Concurrent prophylactic anticoagulation, such as low-dose warfarin, for venous or arterial access device allowed provided PT, PTT, and INR are normal No other concurrent investigational agents No other concurrent anticancer therapy

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (sorafenib tosylate and recombinant interferon alfa)<br>Patients receive oral sorafenib twice daily and interferon alfa subcutaneously three times a week for 8 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity | Drug: sorafenib tosylate<br>* Given orally<br>* Other names: SFN;Biological: recombinant interferon alfa<br>* Given orally<br>* Other names: Roferon-A;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (CR+PR) using RECIST criteria | CR+PR rate will be calculated with exact 90% confidence intervals. | Up to 5 years | 
| Grade 3+ toxicities assessed using NCI CTCAE version 3.0 | Toxicities will be tabulated by type and grade. Toxicity rates will be calculated with exact 90% confidence intervals. | Up to 5 years | 
| Progression-free survival | Kaplan-Meier curves will be used. | Up to 5 years | 
| Overall survival | Kaplan-Meier curves will be used. | Up to 5 years | 
| Duration of response | Kaplan-Meier curves will be used. | From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented , assessed up to 5 years |