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A Phase 1 Study of 5-azacitidine in Combination With Interferon-Alfa 2B in Unresectable or Metastatic Melanoma and Renal Cell Carcinoma

Phase 1
18 Years
Not Enrolling
Recurrent Melanoma, Recurrent Renal Cell Cancer, Stage III Melanoma, Stage IV Melanoma, Stage IV Renal Cell Cancer

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Trial Information

A Phase 1 Study of 5-azacitidine in Combination With Interferon-Alfa 2B in Unresectable or Metastatic Melanoma and Renal Cell Carcinoma


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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Adverse event profile of azacitidine and recombinant interferon alfa-2b in patients with unresectable or metastatic melanoma and renal cell carcinoma

Outcome Description:

Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Outcome Time Frame:

Continuously throughout study

Safety Issue:


Principal Investigator

Mario Sznol

Investigator Role:

Principal Investigator

Investigator Affiliation:

Yale University


United States: Food and Drug Administration

Study ID:




Start Date:

July 2005

Completion Date:

Related Keywords:

  • Recurrent Melanoma
  • Recurrent Renal Cell Cancer
  • Stage III Melanoma
  • Stage IV Melanoma
  • Stage IV Renal Cell Cancer
  • Carcinoma, Renal Cell
  • Melanoma



Yale UniversityNew Haven, Connecticut  06520