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

• ClinicalTrials.gov Identifier: NCT00026221
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Results First Posted: March 17, 2016
• Last Update Posted: March 17, 2016
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Recurrent Melanoma; Stage IV Skin Melanoma	Biological: Recombinant Interferon Alfa; Biological: Bevacizumab	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Bevacizumab and Interferon-Alpha-2b in Metastatic Malignant Melanoma
• Study Start Date: November 2001
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: November 2013

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate [ Time Frame: Up to 2 years ]
   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. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR.
2. Progression-free Survival [ Time Frame: Up to 2 years ]
   Defined as the time from treatment start date until documentation of progressive disease. Evaluated using the new international criteria proposed by the RECIST Committee. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures :

1. Comparison of Plasma Levels of VEGF Following Administration of Bevacizumab Alone or in Combination With IFN-alfa [ Time Frame: At baseline ]
   Analyzed by Enzyme-Linked Immunosorbent Assay (ELISA).VEGF only analyzed at baseline.
2. New Vessel Formation in Patient Tumor Samples [ Time Frame: Up to 2 years ]
   Evaluated using immunohistochemistry.

Other Outcome Measures:

1. Toxicity [ Time Frame: Continuously from the start of treatment to the end of study ]
   Evaluated using the National Cancer Institute (NCI) Common Toxicity Criteria version 2.0.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

Locations

United States, Ohio

University of Cincinnati

Cincinnati, Ohio, United States, 45267

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States, 43210

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: William Carson; Ohio State University Comprehensive Cancer Center

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00026221
• Other Study ID Numbers: NCI-2009-00006; NCI-2009-00006 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000069010; 2001C0185; OSU-01H0185; 0132; NCI-2669; OSU 0132 ( Other Identifier: Ohio State University Comprehensive Cancer Center ); 2669 ( Other Identifier: CTEP ); N01CM62207 ( U.S. NIH Grant/Contract ); R21CA093071 ( U.S. NIH Grant/Contract ); P30CA016058 ( U.S. NIH Grant/Contract )
• First Posted: January 27, 2003
• Results First Posted: March 17, 2016
• Last Update Posted: March 17, 2016
• Last Verified: February 2016

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Interferons; Interferon-alpha; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Antiviral Agents; Anti-Infective Agents; Immunologic Factors