Carboplatin With or Without Decitabine in Treating Patients With Progressive, Advanced Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
- Conditions
- Ovarian CancerPeritoneal Cavity CancerFallopian Tube Cancer
- Interventions
- Registration Number
- NCT00748527
- Lead Sponsor
- Cancer Research UK
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin and decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether carboplatin is more effective with or without decitabine in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
PURPOSE: This randomized phase II trial is studying carboplatin and decitabine to see how well they work compared with carboplatin alone in treating patients with progressive, advanced ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
- Detailed Description
OBJECTIVES:
Primary
* To compare the response rate in patients with progressive, advanced ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer who have methylated hMLH1 DNA in plasma treated with carboplatin with vs without decitabine.
Secondary
* To compare the response rate in all patients (regardless of methylation status) treated with these regimens.
* To compare the progression-free survival and overall survival of patients treated with these regimens.
* To compare the safety and tolerability of these regimens.
* To determine the feasibility of combining decitabine with carboplatin.
* To determine the incidence of hypersensitivity reactions to carboplatin.
* To study the relationship between peak plasma levels of decitabine and global or CpG island specific methylation.
* To study the relationship between global and gene specific methylation in peripheral blood mononuclear cells and response.
Tertiary
* To correlate the methylation status of genes associated with drug resistance detected in plasma DNA with response.
* To determine the sensitivity and specificity of methylation of genes associated with drug resistance detected in plasma DNA as a predictor of methylation status in tumor cells isolated from ascites or tumor biopsy.
* To study methylation and expression of genes in tumor cells isolated from ascites or tumor biopsy before and after treatment with decitabine and/or carboplatin.
* To investigate any correlation between methylation and expression of genes in surrogate tissues, body fluids, or tumor cells and response or progression-free survival.
* To examine markers of cell death in plasma.
* To compare the methylation in tumor taken at the time of presentation vs at the time of treatment.
OUTLINE: This is a multicenter study. Patients are stratified according to prior first-line treatment (platinum alone vs platinum and taxane vs platinum and other combination), WHO performance status (0 vs 1 vs 2), measurable disease criteria (RECIST criteria vs CA-125 criteria vs both), participating center, and the number of prior platinum-based regimens (1 vs 2). Patients are randomized to 1 of 2 treatment arms.
* Arm I: Patients receive carboplatin IV over 30-60 minutes on day 1.
* Arm II: Patients receive decitabine IV over 6 hours on day 1 and carboplatin IV over 30-60 minutes on day 8.
In both arms, treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection periodically for pharmacodynamic studies. Samples are assessed for methylation of hMLH1 by methylation-specific PCR; global DNA methylation by high performance liquid chromatography (HPLC) ; methylation of the MAGE-1A gene promoter by methylation-specific PCR or bisulfite pyrosequencing; and markers of apoptosis by ELISA. Pharmacokinetic studies of decitabine are also performed using blood samples from patients randomized to arm II. Ascitic fluid and/or tumor tissue samples may also be collected for pharmacodynamic studies.
After completion of study treatment, patients are followed at 28 days and then every 2 months thereafter.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 134
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Arm I carboplatin Patients receive carboplatin IV over 30-60 minutes on day 1. Arm II carboplatin Patients receive decitabine IV over 6 hours on day 1 and carboplatin IV over 30-60 minutes on day 8. Arm II decitabine Patients receive decitabine IV over 6 hours on day 1 and carboplatin IV over 30-60 minutes on day 8.
- Primary Outcome Measures
Name Time Method Response rate (partial response [PR] or complete response [CR]) in patients with methylated hMLH1 DNA in plasma as measured by RECIST criteria or CA-125 criteria
- Secondary Outcome Measures
Name Time Method Response rate (PR or CR) in all patients (regardless of methylation status) as measured by RECIST criteria or CA-125 criteria Correlation between response (PR or CR) and global and CpG island specific DNA methylation in peripheral blood mononuclear cells CpG island specific DNA methylation in tumor DNA and expression of genes as measured by RNA or protein assays Progression-free survival and overall survival Adverse events as measured by NCI CTCAE v3.0 Correlation between peak plasma levels of decitabine and global and CpG island specific DNA methylation in peripheral blood mononuclear cells Correlation between response (PR, CR, or stable disease) and CpG island specific DNA methylation in tumor DNA and expression of genes by RNA or protein assays Immunoassays of proteins in plasma Total dose and dose intensity of carboplatin and decitabine Incidence of grade 3-4 hypersensitivity reactions CpG island specific DNA methylation in plasma and tumor DNA Correlation between response (PR or CR) and CpG island specific DNA methylation in plasma DNA CpG island specific DNA methylation in tumor DNA
Trial Locations
- Locations (11)
Leicester Royal Infirmary
🇬🇧Leicester, England, United Kingdom
Hammersmith Hospital
🇬🇧London, England, United Kingdom
Saint Bartholomew's Hospital
🇬🇧London, England, United Kingdom
Weston General Hospital
🇬🇧Weston-super-Mare, England, United Kingdom
Belfast City Hospital Trust Incorporating Belvoir Park Hospital
🇬🇧Belfast, Northern Ireland, United Kingdom
Mount Vernon Cancer Centre at Mount Vernon Hospital
🇬🇧Northwood, England, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, Scotland, United Kingdom
Leeds Cancer Centre at St. James's University Hospital
🇬🇧Leeds, England, United Kingdom
Royal Marsden - London
🇬🇧London, England, United Kingdom
Royal Marsden - Surrey
🇬🇧Sutton, England, United Kingdom
Edinburgh Cancer Centre at Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom