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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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00217542
First Posted: September 22, 2005
Last Update Posted: May 3, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
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.

Condition Intervention Phase
Recurrent Melanoma Recurrent Renal Cell Cancer Stage III Melanoma Stage IV Melanoma Stage IV Renal Cell Cancer Biological: recombinant interferon alfa-2b Drug: amifostine/azacitidine Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of 5-azacitidine in Combination With Interferon-Alfa 2B in Unresectable or Metastatic Melanoma and Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ]
    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) ]
    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 ]
    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.


Secondary Outcome Measures:
  • 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 ]
    Evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.


Enrollment: 42
Study Start Date: July 2005
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Biological: recombinant interferon alfa-2b
Given SC
Other Names:
  • Alfatronol
  • Glucoferon
  • Heberon Alfa
  • IFN alpha-2B
  • Intron A
Drug: amifostine/azacitidine
Given SC

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00217542


Locations
United States, Connecticut
Yale University
New Haven, Connecticut, United States, 06520-8032
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mario Sznol Yale University
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00217542     History of Changes
Other Study ID Numbers: NCI-2009-00152
YALE HIC#27409
YALE-HIC-27409
NCI-7317
CDR0000441640
First Submitted: September 20, 2005
First Posted: September 22, 2005
Last Update Posted: May 3, 2013
Last Verified: May 2013

Additional relevant MeSH terms:
Melanoma
Carcinoma, Renal Cell
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Interferons
Azacitidine
Interferon-alpha
Amifostine
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action