Azacitidine and Recombinant Interferon Alfa-2b in Treating Patients With Stage III or Stage IV Melanoma or Stage IV Kidney Cancer That Cannot Be Removed By Surgery

NCT ID: NCT00217542

Last Updated: 2013-05-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-07-31

Brief Summary

This phase I trial is studying the side effects and best dose of recombinant interferon alfa-2b when given together with azacitidine in treating patients with stage III or stage IV melanoma or stage IV kidney cancer that cannot be removed by surgery. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Recombinant interferon alfa-2b may interfere with the growth of tumor cells. Giving azacitidine together with recombinant interferon alfa-2b may kill more tumor cells.

Detailed Description

OBJECTIVES:

I. Determine the adverse event profile and maximum tolerated dose of interferon alfa-2b when combined with azacitidine in patients with unresectable stage III or IV melanoma or unresectable stage IV renal cell carcinoma.

II. Determine the feasibility of this regimen for future phase II trials.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive azacitidine subcutaneously (SC) once daily on days 1-4 and 15-17 and recombinant interferon alfa-2b SC on days 8, 10, 12, 15, 17, 19, 22, 24, and 26 during course 1. Beginning in course 2 and for all subsequent courses, patients receive azacitidine SC once daily on days 1-3 and 15-17 and interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 total courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of interferon alfa-2b until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 2-4 months.

Conditions

Recurrent Melanoma; Recurrent Renal Cell Cancer; Stage III Melanoma; Stage IV Melanoma; Stage IV Renal Cell Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (chemotherapy, biological therapy)

Patients receive azacitidine SC once daily on days 1-4 and 15-17 and recombinant interferon alfa-2b SC on days 8, 10, 12, 15, 17, 19, 22, 24, and 26 during course 1. Beginning in course 2 and for all subsequent courses, patients receive azacitidine SC once daily on days 1-3 and 15-17 and interferon alfa-2b SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26. Treatment repeats every 28 days for up to 12 total courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

recombinant interferon alfa-2b

Intervention Type: BIOLOGICAL

Given SC

amifostine/azacitidine

Intervention Type: DRUG

Given SC

Interventions

recombinant interferon alfa-2b

Given SC

Intervention Type: BIOLOGICAL

amifostine/azacitidine

Given SC

Intervention Type: DRUG

Other Intervention Names

Alfatronol; Glucoferon; Heberon Alfa; IFN alpha-2B; Intron A

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed diagnosis of 1 of the following:

• Melanoma

• Unresectable stage III disease
• Stage IV disease
• Renal cell carcinoma

• Unresectable and/or stage IV disease
• Measurable disease
• No untreated brain metastases or leptomeningeal disease

• Patients with previously treated brain metastases are eligible provided they have no evidence of progression for ≥ 4 weeks following treatment and do not require steroids
• Performance status - ECOG 0-2
• Performance status - Karnofsky 60-100%
• More than 3 months
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL (may be transfused to this level)
• PT or PTT < 1.5 times upper limit of normal (ULN)
• Bilirubin ≤ 2.0 mg/mL
• AST and ALT ≤ 3 times ULN (5 times ULN for patients with liver metastases)
• Albumin ≥ 3.0 g/dL
• Creatinine ≤ 1.7 mg/dL
• Creatinine clearance ≥ 50 mL/min
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No ventricular cardiac arrhythmia
• No myocardial infarction within the past 3 months
• No dyspnea at rest
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active gastrointestinal bleeding or ulcer disease
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to study agents
• At least 2 weeks since prior immunotherapy
• Prior adjuvant interferon alfa for metastatic disease or in the adjuvant setting allowed
• At least 3 weeks since prior cytotoxic agents (6 weeks for nitrosoureas or mitomycin)
• See Disease Characteristics
• At least 2 weeks since prior hormonal therapy
• At least 1 week since prior and no concurrent steroids
• At least 3 weeks since prior radiotherapy
• At least 2 weeks since prior minor surgery
• At least 3 weeks since prior major surgery
• Recovered from all prior therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy

• 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

Mario Sznol

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale University

New Haven, Connecticut, United States

Countries

United States

Other Identifiers

YALE HIC#27409

Identifier Type: -

Identifier Source: secondary_id

YALE-HIC-27409

Identifier Type: -

Identifier Source: secondary_id

NCI-7317

Identifier Type: -

Identifier Source: secondary_id

CDR0000441640

Identifier Type: -

Identifier Source: secondary_id

NCI-2009-00152

Identifier Type: -

Identifier Source: org_study_id