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
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxicities as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Outcome Description:
The type, frequency, and severity of each toxicity will be reported.
Outcome Time Frame:
At each dose level of PEGIntron and decitabine
Safety Issue:
Yes
Principal Investigator
Wolfram Samlowski
Investigator Role:
Principal Investigator
Investigator Affiliation:
Nevada Cancer Institute-Summerlin Campus
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2009-00295
NCT ID:
NCT00701298
Start Date:
April 2009
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
Name | Location |
|---|---|
| Nevada Cancer Institute-Summerlin Campus | Las Vegas, Nevada 89135 |
