- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00701298
Decitabine With or Without Interferon Alfa-2b in Treating Patients With Unresectable or Metastatic Solid Tumors
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
Study Overview
Status
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Nevada
-
Las Vegas, Nevada, United States, 89135
- Nevada Cancer Institute-Summerlin Campus
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
|
Correlative studies
Given IV
Other Names:
|
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.
|
Correlative studies
Given IV
Other Names:
Given SC
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Up to 28 days
|
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.
|
First 28-day course
|
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.
|
First 28-day course
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Baseline to up to day 1 of course 2
|
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.
|
Baseline to up to day 1 of course 2
|
Complete and partial response rates
Time Frame: Up to 1 year
|
Up to 1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Wolfram Samlowski, Nevada Cancer Institute-Summerlin Campus
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunologic Factors
- Interferons
- Interferon-alpha
- Decitabine
- Interferon alpha-2
- Azacitidine
- Peginterferon alfa-2b
Other Study ID Numbers
- 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)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Unspecified Adult Solid Tumor, Protocol Specific
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingCollection and Storage of Tissue Samples From Patients Undergoing Surgery For Suspected Solid TumorsUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Kantonsspital GraubuendenUnknownUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificSwitzerland
-
National Cancer Institute (NCI)CompletedUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Vanderbilt UniversityNational Cancer Institute (NCI)TerminatedUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
University of ChicagoNational Cancer Institute (NCI)CompletedSirolimus in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed By SurgeryUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)WithdrawnUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol Specific
-
Memorial Sloan Kettering Cancer CenterNational Cancer Institute (NCI)CompletedUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol SpecificUnited States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyWithdrawnUnspecified Childhood Solid Tumor, Protocol Specific | Unspecified Adult Solid Tumor, Protocol Specific | Hematopoietic/Lymphoid CancerUnited States
-
University of Texas Southwestern Medical CenterRecruitingUnspecified Adult Solid Tumor, Protocol SpecificUnited States
Clinical Trials on laboratory biomarker analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
National Cancer Institute (NCI)Recruiting
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingLynch Syndrome | Recurrent Uterine Corpus Carcinoma | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)Not yet recruitingRecurrent Uterine Corpus Carcinoma | Stage III Uterine Corpus Cancer | Stage IV Uterine Corpus CancerUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
-
National Cancer Institute (NCI)Active, not recruitingMalignant NeoplasmUnited States
-
Ohio State University Comprehensive Cancer CenterActive, not recruitingLung Cancer | Radiation Toxicity | Adult Brain TumorUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedRecurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor | Askin TumorUnited States, Canada, Puerto Rico, Australia, New Zealand, Switzerland
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed