Bevacizumab With or Without Interferon Alfa in Treating Patients With Metastatic Malignant Melanoma

NCT ID: NCT00026221

Last Updated: 2016-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-11-30
• Study Completion Date: 2013-11-30

Brief Summary

This randomized phase II trial is studying giving bevacizumab together with interferon alpha to see how well it works compared to giving bevacizumab alone in treating patients with metastatic malignant melanoma. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Interferon alpha may interfere with the growth of the cancer cells and slow the growth of the tumor. Combining bevacizumab with interferon alpha may kill more tumor cells.

Detailed Description

OBJECTIVES:

I. Compare the objective response rate and progression-free survival in patients with metastatic malignant melanoma treated with bevacizumab with or without low- or high-dose interferon alpha.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1. Patients also receive low-dose interferon alpha (IFN-alpha) subcutaneously (SC) on days 1-14.

ARM II: Patients receive bevacizumab as in arm I.

ARM III: Patients receive bevacizumab as in arm I. Patients also receive high-dose IFN-alpha SC on days 1, 3, 5, 8, 10, and 12. In all arms, treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients undergo restaging at the completion of course 12. Patients with stable disease or a clinical response may continue treatment according to their assigned treatment arm for up to 1 year. Patients with stable disease after 1 year of treatment with bevacizumab and IFN-alpha (arms I and III) may continue to receive bevacizumab alone every 21 days (as in arm II) in the absence of disease progression.

Patients are followed every 3 months for 2 years.

Conditions

Recurrent Melanoma; Stage IV Skin Melanoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I (monoclonal antibody and biological therapy)

Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive low-dose interferon alfa (IFN-alpha) SC on days 1-14.

Group Type: EXPERIMENTAL

Recombinant Interferon Alfa

Intervention Type: BIOLOGICAL

Given SC

Bevacizumab

Intervention Type: BIOLOGICAL

Given IV

Arm II (monoclonal antibody)

Patients receive bevacizumab as in arm I.

Group Type: EXPERIMENTAL

Bevacizumab

Intervention Type: BIOLOGICAL

Given IV

Arm III (monoclonal antibody and biological therapy)

Patients receive bevacizumab as in arm I. Patients also receive high-dose IFN-alpha SC on days 1, 3, 5, 8, 10, and 12.

Group Type: EXPERIMENTAL

Recombinant Interferon Alfa

Intervention Type: BIOLOGICAL

Given SC

Bevacizumab

Intervention Type: BIOLOGICAL

Given IV

Interventions

Recombinant Interferon Alfa

Given SC

Intervention Type: BIOLOGICAL

Bevacizumab

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

IFN-A; Avastin; rhuMab-VEGF

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed cutaneous malignant melanoma

• Must meet one of the following criteria:

• Clinical evidence of metastatic disease
• Unresectable regional lymphatic disease
• Extensive in transit recurrent disease
• Measurable disease

• At least 20 mm by conventional techniques OR at least 10 mm by spiral computed tomography (CT) scan
• No known brain metastases
• No ocular melanoma
• Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2
• Performance status - Karnofsky 60-100%
• More than 6 months
• White blood cells (WBC) at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• No clinical evidence of coagulopathy
• Bilirubin =< 2.0 mg/dL (3.0 mg/dL for patients with Gilbert's disease provided patient is stable and asymptomatic)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) no greater than 2.5 times upper limit of normal (ULN)
• Prothrombin time (PT)/International normalized ratio (INR) less than 1.5
• Creatinine =< 1.5 mg/dL
• Creatinine clearance at least 60 mL/min
• Protein < 1,000 mg on 24-hour urine collection for patients with proteinuria >= 1+
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No history of thrombosis (e.g., deep vein thrombosis), unless the following criteria are met:

• INR in normal range (usually 2-3) AND on a stable dose of warfarin or low molecular weight heparin
• No active bleeding or pathologic condition that would confer a high risk of bleeding (e.g., known varices or tumor involving major vessels)
• No uncontrolled hypertension
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No prior allergic reactions to compounds of similar chemical or biologic composition to bevacizumab or interferon alfa
• No ongoing or active infection
• No other concurrent uncontrolled illness
• No psychiatric illness or social situation that would preclude study compliance
• Human immunodeficiency virus (HIV) allowed provided otherwise well
• At least 4 weeks since prior adjuvant interferon alfa
• No prior interferon alfa for metastatic disease
• No prior cytokine therapy for metastatic disease (e.g., high-dose interleukin-2 [IL-2])

• Prior IL-2 allowed for patients randomized to arm III only
• No prior investigational antiangiogenic agents
• No more than 1 prior chemotherapy regimen for metastatic disease
• At least 4 weeks since prior chemotherapy and recovered
• At least 4 weeks since prior radiotherapy and recovered
• No other concurrent investigational agents

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Carson

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

University of Cincinnati

Cincinnati, Ohio, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

NCI-2009-00006

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000069010

Identifier Type: -

Identifier Source: secondary_id

2001C0185

Identifier Type: -

Identifier Source: secondary_id

OSU-01H0185

Identifier Type: -

Identifier Source: secondary_id

0132

Identifier Type: -

Identifier Source: secondary_id

NCI-2669

Identifier Type: -

Identifier Source: secondary_id

OSU 0132

Identifier Type: OTHER

Identifier Source: secondary_id

2669

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM62207

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R21CA093071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA016058

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00006

Identifier Type: -

Identifier Source: org_study_id