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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00098618

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Clear Cell Renal Cell Carcinoma Papillary Renal Cell Carcinoma Recurrent Renal Cell Cancer Stage III Renal Cell Cancer Stage IV Renal Cell Cancer	Drug: sorafenib tosylate Biological: recombinant interferon alfa Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

Determine the feasibility and tolerability of sorafenib and interferon alfa in patients with locally advanced or metastatic renal cell carcinoma.
Determine the response rate (complete response and partial response) in patients treated with this regimen.

SECONDARY OBJECTIVES:

Determine the progression-free survival and response duration of patients treated with this regimen.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2004

Actual Primary Completion Date :

Jan 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (sorafenib tosylate and recombinant interferon alfa) 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 Given orally Other Names: BAY 43-9006 BAY 43-9006 Tosylate Salt BAY 54-9085 Nexavar SFN Biological: recombinant interferon alfa Given orally Other Names: Alferon N alpha interferon IFN-A Intron A Roferon-A Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (sorafenib tosylate and recombinant interferon alfa)

Drug: sorafenib tosylate

Given orally

Other Names:

BAY 43-9006

BAY 43-9006 Tosylate Salt

BAY 54-9085

Nexavar

SFN

Biological: recombinant interferon alfa

Given orally

Other Names:

Alferon N

alpha interferon

IFN-A

Intron A

Roferon-A

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Overall response rate (CR+PR) using RECIST criteria [Up to 5 years]
CR+PR rate will be calculated with exact 90% confidence intervals.
Grade 3+ toxicities assessed using NCI CTCAE version 3.0 [Up to 5 years]
Toxicities will be tabulated by type and grade. Toxicity rates will be calculated with exact 90% confidence intervals.
Progression-free survival [Up to 5 years]
Kaplan-Meier curves will be used.
Overall survival [Up to 5 years]
Kaplan-Meier curves will be used.
Duration of response [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]
Kaplan-Meier curves will be used.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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