Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	Over 18	NCI	OSU-01H0185 NCI-2669, NCT00026221, 2669

Objectives

1. 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 alfa.

Entry Criteria

Disease Characteristics:

• 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 CT scan



• No known brain metastases



• No ocular melanoma

Prior/Concurrent Therapy:

Biologic therapy:

• 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

Chemotherapy:

• No more than 1 prior chemotherapy regimen for metastatic disease
• At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• Not specified

Other:

• No other concurrent investigational agents

Patient Characteristics:

Age:

• Over 18

Performance status:

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy:

• More than 6 months

Hematopoietic:

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• No clinical evidence of coagulopathy

Hepatic:

• Bilirubin ≤ 2.0 mg/dL (3.0 mg/dL for patients with Gilbert's disease provided patient is stable and asymptomatic)
• AST/ALT no greater than 2.5 times ULN
• PT/INR less than 1.5

Renal:

• Creatinine ≤ 1.5 mg/dL

  OR

• Creatinine clearance at least 60 mL/min
• Protein < 1,000 mg on 24-hour urine collection for patients with proteinuria ≥ 1+

Cardiovascular:

• 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

Other:

• 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
• HIV allowed provided otherwise well

Expected Enrollment

A total of 65 patients will be accrued for this study within 6-10 months.

Outcomes

Response rate every 3 months

Progression-free survival every 3 months

Outline

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

• Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive low-dose interferon alfa (IFN-α) 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-α 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-α (arms I and III) may continue to receive bevacizumab alone (as in arm II) in the absence of disease progression.

Patients are followed every 3 months for 2 years.

Trial Contact Information

Trial Lead Organizations

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

William Carson, MD, Protocol chair		Ph: 614-292-5819 Email: william.carson@osumc.edu

U.S.A.
Ohio
	Columbus
	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
		Ohio State University Cancer Clinical Trial Matching Service	Ph:  866-627-7616
			Email: osu@emergingmed.com

Registry Information
Official Title		A Phase 2 Study Of Bevacizumab And Interferon-Alpha-2b In Metastatic Malignant Melanoma
Trial Start Date		2001-12-01
Trial Completion Date		2002-09-27 (estimated)
Registered in ClinicalTrials.gov		NCT00026221
Date Submitted to PDQ		2001-08-30
Information Last Verified		2007-10-05
NCI Grant/Contract Number		CA16058, CA93071