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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00217542
First received: September 20, 2005
Last updated: May 1, 2013
Last verified: May 2013

September 20, 2005
May 1, 2013
July 2005
July 2008   (final data collection date for primary outcome measure)
  • Adverse event profile of azacitidine and recombinant interferon alfa-2b in patients with unresectable or metastatic melanoma and renal cell carcinoma [ Time Frame: Continuously throughout study ] [ Designated as safety issue: Yes ]
    Graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
  • Maximum tolerated dose of recombinant interferon alfa-2b when administered in combination with 5-azacitidine [ Time Frame: Course 1 (4 weeks) ] [ Designated as safety issue: Yes ]
    Toxicity will be graded according to the NCI CTCAE version 3.0. The MTD is the highest dose level in which < 2 patients of 6 develop first cycle DLT.
  • Correlation of promoter methylation with the level of expression of the genes [ Time Frame: Day 5 or 8 and 24 or 26 of course 1 ] [ Designated as safety issue: No ]
    Determined by Western blotting, immunohistochemistry, and/or RT-PCR. We will use Western blot analysis when antibodies are available and semi-quantitative RT-PCR in cases where antibodies are not available.
Not Provided
Complete list of historical versions of study NCT00217542 on ClinicalTrials.gov Archive Site
Response rate of giving recombinant interferon alfa-2b when administered in combination with 5-azacitidine in patients with metastatic melanoma and renal cell carcinoma [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
Evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
Not Provided
Not Provided
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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
A Phase 1 Study of 5-azacitidine in Combination With Interferon-Alfa 2B in Unresectable or Metastatic Melanoma and Renal Cell Carcinoma

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Melanoma
  • Recurrent Renal Cell Cancer
  • Stage III Melanoma
  • Stage IV Melanoma
  • Stage IV Renal Cell Cancer
  • Biological: recombinant interferon alfa-2b
    Given SC
    Other Names:
    • Alfatronol
    • Glucoferon
    • Heberon Alfa
    • IFN alpha-2B
    • Intron A
  • Drug: amifostine/azacitidine
    Given SC
Experimental: 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.
Interventions:
  • Biological: recombinant interferon alfa-2b
  • Drug: amifostine/azacitidine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
42
Not Provided
July 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00217542
NCI-2009-00152, YALE HIC#27409, YALE-HIC-27409, NCI-7317, CDR0000441640
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Mario Sznol Yale University
National Cancer Institute (NCI)
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP