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Sponsors and Collaborators: |
Indiana University School of Medicine MGI PHARMA, Inc. |
Information provided by: | Indiana University |
ClinicalTrials.gov Identifier: | NCT00477386 |
Based on these pre-clinical data, which were generated by our group, we propose to test in a phase I/II clinical trial the following hypothesis: demethylation induced by decitabine results in re-sensitization to platinum in recurrent ovarian cancer.
To test this hypothesis, we 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 I/II trial to determine the safety and the biologic activity of the Decitabine/Carboplatin combination.
We will determine whether Carboplatin can be safely combined with Decitabine, the optimal dose schedule and we will define whether at this dosage, the regimen is biologically active (i.e. induces demethylation of target genes).
In the second part of the trial, we will determine the clinical activity of the combination in a population of patients with platinum-resistant ovarian cancer.
Condition | Intervention | Phase |
Ovarian Cancer |
Drug: decitabine |
Phase I Phase II |
MedlinePlus related topics: | Cancer Ovarian Cancer |
ChemIDplus related topics: | Carboplatin 5-Aza-2'-deoxycytidine |
Study Type: | Interventional |
Study Design: | Treatment, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study |
Official Title: | Phase I/II Trial of Decitabine as a Sensitizer to Carboplatin in Platinum Resistant Recurrent Ovarian Cancer |
Estimated Enrollment: | 29 |
Study Start Date: | July 2007 |
Estimated Study Completion Date: | December 2011 |
Estimated Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
Decitabine dose will be escalated as follows.
Dose level 1: 10mg/m2 IV QD X 5 days Dose level 2: 20mg/m2 IV QD X 5 days Dose level -1: Carboplatin AUC 4.
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 AUC of 5. The maximum dose of Decitabine (20 mg/m2) is based on the results of the 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 mg/m2 IV 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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
• Have recurrent epithelial ovarian cancer, primary peritoneal carcinomatosis or fallopian tube cancer.
Have measurable disease according to RECIST or detectable disease.
Have acceptable organ function, as evidenced by laboratory data:
Exclusion Criteria:
• Not have participated in any clinical trial involving conventional or investigational drugs or devices within the previous 3 weeks.
Contact: Nancy Menning, RN | 317-274-1658 | nmenning@iupui.edu |
Contact: Daniela Matei, M.D. | 317-278-0070 | dmatei@iupui.edu |
United States, Indiana | |||||
Indiana University Cancer Center | Not yet recruiting | ||||
Indianapolis, Indiana, United States, 46202 | |||||
Principal Investigator: Daniela Matei, MD | |||||
Indiana University Cancer Center | Recruiting | ||||
Indianapolis, Indiana, United States, 46202 | |||||
Contact: Nancy Menning, RN 317-274-1658 nmenning@iupui.edu | |||||
Contact: Daniela Matei, MD 317-278-0080 dmatei@iupui.edu | |||||
Principal Investigator: Daniela Matei, MD |
Indiana University School of Medicine |
MGI PHARMA, Inc. |
Principal Investigator: | Daniela Matei, MD | Indiana University |
Indiana University Cancer Center website 
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Responsible Party: | Indiana University Cancer Center ( Daniela Matei, MD/ Principal Investigator ) |
Study ID Numbers: | 0704-07 IUCRO-0185 |
First Received: | May 21, 2007 |
Last Updated: | July 30, 2008 |
ClinicalTrials.gov Identifier: | NCT00477386 |
Health Authority: | United States: Food and Drug Administration |
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