Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

RATIONALE: Biological therapies, such as interferon alfa-2b, may interfere with the growth of tumor cells. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. It is not yet known whether interferon alfa-2b is more effective with or without bevacizumab in treating advanced renal cell carcinoma (kidney cancer).

PURPOSE: This randomized phase III trial is studying interferon alfa-2b and bevacizumab to see how well they work compared to interferon alfa-2b alone in treating patients with advanced renal cell carcinoma.

Further Study Information

OBJECTIVES:

Primary

• Compare the overall survival of patients with advanced renal cell carcinoma treated with interferon alfa-2b alone or interferon alfa-2b with bevacizumab.

Secondary

• Compare the time to disease progression and objective response rates in patients treated with these regimens.

• Determine the toxicity of interferon alfa-2b in combination with bevacizumab in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior nephrectomy (yes vs no) and number of risk factors for disease progression (0 vs 1-2 vs 3 or more). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive interferon alfa-2b subcutaneously (SC) three times a week.

• Arm II: Patients receive interferon alfa-2b as in arm I and bevacizumab IV over 30-90 minutes on days 1 and 15.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then annually for up to 10 years after study entry.

PROJECTED ACCRUAL: A total of 700 patients (350 per treatment arm) will be accrued for this study within 3 years.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma (RCC)

• Conventional clear cell carcinoma

• Metastatic or unresectable disease

• The following characteristics and cellular types are excluded:

• True papillary

• Sarcomatoid features without a clear cell component

• Chromophobe

• Oncocytoma

• Collecting duct tumor

• Transitional cell carcinoma

• Measurable or nonmeasurable disease, including any of the following:

• Unidimensionally measurable lesion ≥ 20 mm by conventional techniques (e.g., physical exam or chest x-ray) OR 10 mm by spiral CT scan or MRI

• The following are considered nonmeasurable disease:

• Small lesions

• Bone lesions

• Leptomeningeal disease

• Ascites

• Pleural/pericardial effusion

• Lymphangitis cutis/pulmonis

• Abdominal masses that are not confirmed and followed by imaging techniques

• Cystic lesions

• Irradiated lesions, unless progression is documented after radiotherapy

• RCC paraffin tissue blocks or unstained slides must be available

• No evidence of prior or concurrent CNS metastases by MRI or CT scan

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• No history of clinically significant bleeding

Hepatic

• AST/ALT ≤ 2.5 times upper limit of normal (ULN)

• Alkaline phosphatase ≤ 2.5 times ULN

• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

• No proteinuria > 1+

• Proteinuria ≥ 2+ allowed provided protein is < 2 g/24-hour urine collection

Cardiovascular

• No deep venous thrombosis within the past year

• No cerebrovascular accident within the past year

• No peripheral vascular disease with claudication on < 1 block

• No uncontrolled hypertension defined as blood pressure ≥160 mm Hg (systolic) and/or ≥ 90 mm Hg (diastolic) while on medication

• No New York Heart Association class II-IV congestive heart failure

• No angina pectoris requiring nitrate therapy

• No myocardial infarction within the past 6 months

• No other significant cardiovascular disease

Pulmonary

• No pulmonary embolus within the past year

• No ongoing hemoptysis

Other

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after study treatment

• No preexisting thyroid abnormality in which normal thyroid function cannot be maintained by medication

• No delayed wound healing, ulcers, or bone fractures

• No uncontrolled psychiatric disorder

• No other currently active* malignancy except nonmelanoma skin cancer NOTE: *Disease is not considered currently active if patient completed anticancer therapy and is considered to have < 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior systemic immunotherapy for RCC

• No prior thalidomide, anti-vascular endothelial growth factor (VEGF) therapy, VEGF receptor inhibitors, or antiangiogenic treatment of any kind

• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

Chemotherapy

• No prior systemic chemotherapy for RCC

• No concurrent chemotherapy

Endocrine therapy

• No concurrent systemic corticosteroid therapy except the following:

• Topical and inhaled steroids

• Replacement therapy for adrenal insufficiency

• No concurrent hormones except those administered for nondisease-related conditions (e.g., insulin for diabetes)

Radiotherapy

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy and recovered

• Prior palliative radiotherapy to metastatic lesions allowed provided at least 1 measurable or nonmeasurable lesion remains untreated

• No concurrent palliative radiotherapy

Surgery

• At least 4 weeks since prior major surgery and recovered

Other

• No other prior systemic investigational therapy for RCC

• No other prior adjuvant or neoadjuvant systemic therapy for RCC

• No concurrent full-dose oral or parenteral anticoagulation* NOTE: *Low-dose (1 mg) warfarin for maintenance of catheter patency and/or daily prophylactic aspirin is allowed

Trial Contact Information

Trial Lead Organizations/Sponsors

Cancer and Leukemia Group B

Brian I. Rini, MD

Study Chair

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00072046
Information obtained from ClinicalTrials.gov on November 20, 2012

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