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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00026221
First received: November 9, 2001
Last updated: November 25, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Recurrent Melanoma
Stage IV Skin Melanoma
Biological: Recombinant Interferon Alfa
Biological: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Bevacizumab and Interferon-alpha-2b in Metastatic Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response rate [ Time Frame: Every 12 weeks ] [ Designated as safety issue: No ]
    Measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. 95% confidence interval will be calculated.

  • Toxicity [ Time Frame: Continuously from the start of treatment to the end of study ] [ Designated as safety issue: No ]
    Evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria version 2.0.

  • Progression-free survival [ Time Frame: Every 12 weeks ] [ Designated as safety issue: No ]
    Defined as the time from treatment start date until documentation of progressive disease. Evaluated using the new international criteria proposed by the RECIST Committee.


Secondary Outcome Measures:
  • Comparison of plasma levels of VEGF following administration of bevacizumab alone or in combination with IFN-alfa [ Time Frame: At weeks 1, 3, 5, 7, 9, and 11 ] [ Designated as safety issue: No ]
    Analyzed by Enzyme-Linked Immunosorbent Assay (ELISA). Compared using the Wilcoxon Rank Sum Test.

  • New vessel formation in patient tumor samples [ Time Frame: Every 12 weeks ] [ Designated as safety issue: No ]
    Evaluated using immunohistochemistry.


Estimated Enrollment: 65
Study Start Date: November 2001
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: Recombinant Interferon Alfa
Given SC
Other Name: IFN-A
Biological: Bevacizumab
Given IV
Other Names:
  • Avastin
  • rhuMab-VEGF
Experimental: Arm II (monoclonal antibody)
Patients receive bevacizumab as in arm I.
Biological: Bevacizumab
Given IV
Other Names:
  • Avastin
  • rhuMab-VEGF
Experimental: 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.
Biological: Recombinant Interferon Alfa
Given SC
Other Name: IFN-A
Biological: Bevacizumab
Given IV
Other Names:
  • Avastin
  • rhuMab-VEGF

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00026221

Locations
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: William Carson Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00026221     History of Changes
Other Study ID Numbers: NCI-2009-00006, NCI-2009-00006, CDR0000069010, 2001C0185, 0132, OSU-01H0185, NCI-2669, OSU 0132, 2669, P30CA016058, N01CM62207, R21CA093071
Study First Received: November 9, 2001
Last Updated: November 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Bevacizumab
Interferon-alpha
Interferons
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014