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

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Active	18 and over	NCI	YALE-HIC-27409 7317, NCI-7317, NCT00217542

Objectives

1. 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.
2. Determine the feasibility of this regimen for future phase II trials.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• At least 2 weeks since prior immunotherapy
• Prior adjuvant interferon alfa for metastatic disease or in the adjuvant setting allowed

Chemotherapy

• At least 3 weeks since prior cytotoxic agents (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• See Disease Characteristics
• At least 2 weeks since prior hormonal therapy
• At least 1 week since prior and no concurrent steroids

Radiotherapy

• At least 3 weeks since prior radiotherapy

Surgery

• At least 2 weeks since prior minor surgery
• At least 3 weeks since prior major surgery

Other

• Recovered from all prior therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No other concurrent anticancer therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9.0 g/dL (may be transfused to this level)

Hepatic

• 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

Renal

• Creatinine ≤ 1.7 mg/dL

  OR

• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No ventricular cardiac arrhythmia
• No myocardial infarction within the past 3 months

Pulmonary

• No dyspnea at rest

Other

• 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

Expected Enrollment

A total of 3-42 patients will be accrued for this study within 1-21 months.

Outline

This is a dose-escalation, multicenter study.

Patients receive azacitidine subcutaneously (SC) once daily on days 1-4 and 15-17 and 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.

Trial Contact Information

Trial Lead Organizations

Yale Cancer Center

Mario Sznol, MD, Protocol chair		Ph: 203-785-6221; 866-925-3226

U.S.A.
Connecticut
	New Haven
	Yale Cancer Center
		Clinical Trials Office - Yale Cancer Center	Ph:  203-785-5702
Ohio
	Cleveland
	Cleveland Clinic Taussig Cancer Center
		Clinical Trials Office - Cleveland Clinic Taussig Cancer Center	Ph:  866-223-8100

Registry Information
Official Title		A Phase I Study of 5-Azacitidine in Combination with Interferon-Alfa 2B in Unresectable or Metastatic Melanoma and Renal Cell Carcinoma
Trial Start Date		2005-08-01
Trial Completion Date		2006-09-25 (estimated)
Registered in ClinicalTrials.gov		NCT00217542
Date Submitted to PDQ		2005-07-21
Information Last Verified		2006-11-16
NCI Grant/Contract Number		CA16359