Ignite Creation Date:
2024-05-05 @ 5:31 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00477386
Status:
COMPLETED
Last Update Posted:
2014-09-25
First Post:
2007-05-21
Brief Title:
Trial of Decitabine as a Sensitizer to Carboplatin in Platinum Resistant Recurrent Ovarian Cancer
Sponsor:
Indiana University
Organization:
Indiana University
Study Overview
Official Title:
Phase III Trial of Decitabine as a Sensitizer to Carboplatin in Platinum Resistant Recurrent Ovarian Cancer
Status:
COMPLETED
Status Verified Date:
2014-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Based on these pre-clinical data which were generated by our group the investigators propose to test in a phase III clinical trial the following hypothesis demethylation induced by decitabine results in re-sensitization to platinum in recurrent ovarian cancer
To test this hypothesis the investigators will treat patients with recurrent ovarian cancer platinum resistant recurrence within 6 months from platinum therapy or platinum-refractory no response to platinum with a combination consisting of decitabine and carboplatin
This will be an institutional open label phase III trial to determine the safety and the biologic activity of the DecitabineCarboplatin combination
The investigators will determine whether Carboplatin can be safely combined with Decitabine the optimal dose schedule and the investigators will define whether at this dosage the regimen is biologically active ie induces demethylation of target genes
In the second part of the trial the investigators will determine the clinical activity of the combination in a population of patients with platinum-resistant ovarian cancer
To test this hypothesis the investigators will treat patients with recurrent ovarian cancer platinum resistant recurrence within 6 months from platinum therapy or platinum-refractory no response to platinum with a combination consisting of decitabine and carboplatin
This will be an institutional open label phase III trial to determine the safety and the biologic activity of the DecitabineCarboplatin combination
The investigators will determine whether Carboplatin can be safely combined with Decitabine the optimal dose schedule and the investigators will define whether at this dosage the regimen is biologically active ie induces demethylation of target genes
In the second part of the trial the investigators will determine the clinical activity of the combination in a population of patients with platinum-resistant ovarian cancer
Detailed Description:
Decitabine at escalating dose levels will be given IV X 5 days followed by Carboplatin given IV on Day 8 at a dose corresponding to an area under curve AUC of 5 The maximum dose of Decitabine 20 mgm2 is based on the results of the myelodysplastic syndrome MDS clinical trial that demonstrated biological and clinical efficacy at this dose 15-17 It is recognized that higher doses of decitabine can be administered myelotoxicity being the most significant adverse event This protocol will assess the lower less toxic but biologically active dose
Decitabine dose will be escalated as follows
Dose level -1 5 mgm2 IV per day QD X 5 days Dose level 1 10mgm2 IV QD X 5 days Dose level 2 20mgm2 IV QD X 5 days
Each cycle will consist of 28 days with delays to allow blood count recovery Correlative blood draws will occur on Day1 baseline and on Day 8 before Carboplatin for cycle 1 and 2
The escalation phase will follow the standard 33 design That is patients will be accrued to each dose level in cohorts of up to 3-6 patients Escalation will continue until a DLT is observed the highest dose-level is reached or medical judgment indicates The goal of the phase I cohort is to ensure the safety and tolerability of the combination not to define the maximum tolerated dose
An initial 3 patients will be enrolled at dose level 1 If all 3 patients in dose level 1 complete 4 weeks of therapy without dose limiting toxicity DLT the study will proceed to enroll 3 patients at dose level 2 If all 3 patients in dose level 2 complete 4 weeks of therapy without DLT we will accrue 3 more to ensure that only 0 or 1 of 6 have a DLT and then proceed to the phase II cohort As dose level 2 represents full doses of both agents there will be no further dose escalation beyond dose level 2
Decitabine dose will be escalated as follows
Dose level -1 5 mgm2 IV per day QD X 5 days Dose level 1 10mgm2 IV QD X 5 days Dose level 2 20mgm2 IV QD X 5 days
Each cycle will consist of 28 days with delays to allow blood count recovery Correlative blood draws will occur on Day1 baseline and on Day 8 before Carboplatin for cycle 1 and 2
The escalation phase will follow the standard 33 design That is patients will be accrued to each dose level in cohorts of up to 3-6 patients Escalation will continue until a DLT is observed the highest dose-level is reached or medical judgment indicates The goal of the phase I cohort is to ensure the safety and tolerability of the combination not to define the maximum tolerated dose
An initial 3 patients will be enrolled at dose level 1 If all 3 patients in dose level 1 complete 4 weeks of therapy without dose limiting toxicity DLT the study will proceed to enroll 3 patients at dose level 2 If all 3 patients in dose level 2 complete 4 weeks of therapy without DLT we will accrue 3 more to ensure that only 0 or 1 of 6 have a DLT and then proceed to the phase II cohort As dose level 2 represents full doses of both agents there will be no further dose escalation beyond dose level 2
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None