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

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.
 
ClinicalTrials.gov Identifier: NCT00701298
Recruitment Status : Terminated
First Posted : June 19, 2008
Last Update Posted : February 24, 2014
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE June 18, 2008
First Posted Date  ICMJE June 19, 2008
Last Update Posted Date February 24, 2014
Study Start Date  ICMJE April 2009
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2014)
  • 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 ]
    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 ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 18, 2008)
  • Toxicities
  • Dose-limiting toxicity and maximum tolerated dose of pegylated interferon alfa-2b when given with decitabine
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2014)
  • Global (genomic) DNA methylation changes by high-performance liquid chromatography (HPLC) [ Time Frame: Baseline to up to day 1 of course 2 ]
    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 ]
    Repeated measures analysis of variance and other linear modeling techniques will be used.
  • Complete and partial response rates [ Time Frame: Up to 1 year ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2008)
  • Changes in global DNA methylation
  • Changes in Mage-1 mRNA and protein expression, DNMT-1 levels, p53 induction, 2'5'-oligoadenylate synthesis, MxA, and HLA class I levels
  • Complete response and partial response
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Decitabine With or Without Interferon Alfa-2b in Treating Patients With Unresectable or Metastatic Solid Tumors
Official Title  ICMJE 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
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unspecified Adult Solid Tumor, Protocol Specific
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: decitabine
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: peginterferon alfa-2b
    • Drug: decitabine
    • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 18, 2008)
30
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00701298
Other Study ID Numbers  ICMJE NCI-2009-00295
NCI-2009-00295 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000597624
NVCI-0725
NVCI 07-25 ( Other Identifier: Nevada Cancer Institute-Summerlin Campus )
8224 ( Other Identifier: CTEP )
R21CA122270 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Wolfram Samlowski Nevada Cancer Institute-Summerlin Campus
PRS Account National Cancer Institute (NCI)
Verification Date October 2011

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