Phase I/II Trial of Decitabine as a Sensitizer to Carboplatin in Platinum Resistant Recurrent Ovarian Cancer
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 mg/m2) 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
Decitabine dose will be escalated as follows.
Dose level -1: 5 mg/m2 IV per day (QD) X 5 days Dose level 1: 10mg/m2 IV QD X 5 days Dose
level 2: 20mg/m2 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 3+3 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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I: Determine the safety & tolerability of decitabine IV qd x 5d ac Carbo on D8 in pts w/ recurrent epithelial Ov Ca, platinum-resistant or refractory. Phase II: Assess the objective response via RECIST in pts trtd w/ Decitabine & Carbo
RECIST = Response Evaluation Criteria in Solid Tumors
Daniela Matei, MD
United States: Institutional Review Board
|Indiana University Cancer Center||Indianapolis, Indiana 46202-5265|