Decitabine With or Without Interferon Alfa-2b in Treating Patients With Unresectable or Metastatic Solid Tumors

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00701298
First received: June 18, 2008
Last updated: February 21, 2014
Last verified: October 2011
  Purpose

This phase I trial is studying the side effects of decitabine when given together with or without interferon alfa-2b, and the best dose of interferon alfa-2b, in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as interferon alfa-2b, may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether decitabine is more effective when given with or without interferon alfa-2b in treating solid tumors.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Biological: peginterferon alfa-2b
Drug: decitabine
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Inhibition of DNA Methylation by 1-Hr Infusion of 5-aza-2'-Deoxycitidine (Decitabine) x 10 Days (M-F) With Escalating Doses of Sub-Q Pegylated (PEG) Interferon-alpha 2B (PEG-Intron): A Phase I Study With Molecular Correlates

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Toxicities as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
    The type, frequency, and severity of each toxicity will be reported.

  • Dose-limiting toxicity (DLT) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0 [ Time Frame: First 28-day course ] [ Designated as safety issue: Yes ]
    DLT is defined as grade III drug-related non hematologic and/or grade IV drug-related hematologic toxicity.

  • Maximum-tolerated dose (MTD) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0 [ Time Frame: First 28-day course ] [ Designated as safety issue: Yes ]
    The MTD will be the dose level where not more than 1 case of a specific grade III-IV drug-related toxicity is observed, and either 2+toxicities have been observed at the next highest dose level, or the maximum dose-level of PEG-Intron has been reached.


Secondary Outcome Measures:
  • Global (genomic) DNA methylation changes by high-performance liquid chromatography (HPLC) [ Time Frame: Baseline to up to day 1 of course 2 ] [ Designated as safety issue: No ]
    Repeated measures analysis of variance and other linear modeling techniques will be used.

  • Changes in expression of methylation-regulated genes in human biological tissues [ Time Frame: Baseline to up to day 1 of course 2 ] [ Designated as safety issue: No ]
    Repeated measures analysis of variance and other linear modeling techniques will be used.

  • Complete and partial response rates [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: April 2009
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1 (chemotherapy)
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients whose disease is not responding after the first course may crossover to group 2.
Drug: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Other: laboratory biomarker analysis
Correlative studies
Experimental: Group 2 (chemotherapy and antineoplastic agent)
Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Biological: peginterferon alfa-2b
Given SC
Other Names:
  • PEG-IFN alfa-2b
  • pegylated interferon alfa-2b
  • polyethylene glycol IFN-A2b
Drug: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess toxicities of decitabine plus escalating doses of pegylated interferon alfa-2b (PEG-Intron) in patients with metastatic solid tumor.

II. To identify the dose-limiting toxicity of decitabine in combination with escalating doses of pegylated interferon alfa-2b in these patients.

III. To identify the maximum tolerated dose of pegylated interferon alfa-2b in combination with decitabine in these patients.

SECONDARY OBJECTIVES:

I. To evaluate pretreatment and post-treatment blood and tumor samples to identify changes in global (genomic) DNA methylation.

II. To evaluate pretreatment and post-treatment blood, skin and tumor samples to identify changes in Mage-1 mRNA and protein expression, DNMT-1 levels (due to sequestration by 5-azacytidine), p53 induction (evidence of DNA damage response), as well as changes in levels of 2'5'-oligoadenylate synthesis, MxA and HLA class I as indicators of interferon response.

III. To evaluate complete and partial response rates in patients receiving decitabine in combination with escalating doses of pegylated interferon alfa-2b.

OUTLINE:

This is a dose-escalation study of pegylated interferon alfa-2b. Patients are assigned to 1 of 2 treatment groups.

GROUP 1 (control): Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression after the first course of treatment may crossover to receive treatment in group 2.

GROUP 2: Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22.

Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample, normal skin, and tissue biopsy collection at baseline and periodically during study. Blood, normal skin, and tissue samples are analyzed for global (genomic) DNA methylation (gene-promoter methylation, gene and protein expression, p53 induction by DNA damage) and interferon levels by high-performance (pressure) liquid chromatography and PCR methylation assays, and for pharmacodynamic studies.

After completion of study treatment, patients are followed at 28 days and then every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy-proven solid tumor

    • Metastatic or unresectable disease
  • Tumor amenable to biopsy
  • No curative or more effective treatment for this disease exists, in the opinion of the investigator
  • Measurable disease by scans as assessed by RECIST criteria
  • No untreated brain metastasis

    • No longer receiving steroid therapy for previously treated brain metastasis
  • Zubrod performance status of 0-2
  • Bilirubin ≤ 1.5 times upper limit normal (ULN)
  • SGOT or SGPT ≤ 2.5 times ULN (≤ 5 ULN if hepatic metastases present)
  • Serum creatinine ≤ 1.5 times ULN
  • Creatinine clearance ≥ 50 mL/min
  • ANC > 1,500/μL
  • Platelet count > 100,000/μL
  • Hemoglobin > 9 g/dL (transfusion allowed)
  • No NYHA class III-IV cardiac problems (e.g., congestive heart failure or myocardial infarction within the past 2 months)
  • No severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection [e.g., HIV])
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for 3 months after completion of study therapy
  • Willing to undergo biopsies
  • No medical or psychological conditions that, in the opinion of the investigator, may preclude the patient's ability to tolerate or complete the treatment, or to grant reliable informed consent
  • No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I, II, or III cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
  • No prior extensive pelvic irradiation or prolonged nucleoside analogue pretreatment
  • At least 28 days since prior and no concurrent chemotherapy, radiotherapy, surgery, biological therapy, anticancer agent, or other investigational drug
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00701298

Locations
United States, Nevada
Nevada Cancer Institute-Summerlin Campus
Las Vegas, Nevada, United States, 89135
Sponsors and Collaborators
Investigators
Principal Investigator: Wolfram Samlowski Nevada Cancer Institute-Summerlin Campus
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00701298     History of Changes
Other Study ID Numbers: NCI-2009-00295, NCI-2009-00295, CDR0000597624, NVCI-0725, NVCI 07-25, 8224, R21CA122270
Study First Received: June 18, 2008
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Decitabine
Interferons
Interferon-alpha
Peginterferon alfa-2b
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014