A Phase 2 Study of Bevacizumab and Interferon-alpha-2b in Metastatic Malignant Melanoma
18 Years
N/A
Both
Recurrent Melanoma, Stage IV Melanoma
Trial Information
A Phase 2 Study of Bevacizumab and Interferon-alpha-2b in Metastatic Malignant Melanoma
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Objective response rate
Outcome Description:
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.
Outcome Time Frame:
Every 12 weeks
Safety Issue:
No
Principal Investigator
William Carson
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ohio State University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00006
NCT ID:
NCT00026221
Start Date:
November 2001
Completion Date:
Related Keywords:
- Recurrent Melanoma
- Stage IV Melanoma
- Melanoma
Name | Location |
|---|---|
| Ohio State University Medical Center | Columbus, Ohio 43210 |
