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

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

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.

Study Overview

• Status: Terminated
• Conditions: Clear Cell Renal Cell Carcinoma; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer; Recurrent Renal Cell Cancer; Papillary Renal Cell Carcinoma
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: sorafenib tosylate; Biological: recombinant interferon alfa

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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	Other: laboratory biomarker analysis; Correlative studies; 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: Roferon-A; Intron A; alpha interferon; IFN-A; Alferon N

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Daniel George, Duke University

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): January 1, 2006

Study Registration Dates

• First Submitted: December 7, 2004
• First Submitted That Met QC Criteria: December 7, 2004
• First Posted (Estimate): December 8, 2004

Study Record Updates

• Last Update Posted (Estimate): July 2, 2013
• Last Update Submitted That Met QC Criteria: July 1, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Interferons; Interferon-alpha; Sorafenib; Interferon alpha-2
• Other Study ID Numbers: NCI-2012-02638; U01CA099118 (U.S. NIH Grant/Contract); 6258-04-9R0; NCI-6553; CDR0000398171