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Phase I/II Trial of Decitabine as a Sensitizer to Carboplatin in Platinum Resistant Recurrent Ovarian Cancer

Phase 1/Phase 2
18 Years
Open (Enrolling)
Ovarian Cancer

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Trial Information

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
active dose.

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.

Inclusion Criteria:

- Have recurrent epithelial ovarian cancer, primary peritoneal carcinomatosis or
fallopian tube cancer.

- Have platinum-resistant (recurrence within 6 months of a platinum-containing regimen)
or platinum refractory (progression while on platinum) disease

- Have measurable disease according to RECIST or detectable disease.

- Measurable disease is defined as the presence of at least one uni-dimensionally
measurable lesion greater than or equal to 20 mm by conventional techniques,
including palpation, plain x-ray, CT scan or MRI, or greater than or equal to 10
mm by spiral CT scan.

- Detectable disease is defined in a patient as one who does not have measurable
disease but has at least one of the following conditions: 1) Baseline values of
cancer antigen 125 (CA-125) at least twice the upper limit of normal; 2) Ascites
and/or pleural effusion attributed to tumor; 3) solid and/or cystic
abnormalities on radiographic imaging that do not meet RECIST definitions for
target lesions.

- ≥18 years of age.

- Give written, informed consent for participation in the protocol.

- Be at least 4 weeks from last treatment to allow recovery from prior toxicity (with
the exception of hormonal therapy, where a 1-week wash-out period and radiation
therapy where a 3-week wash-out period are sufficient). Patients coming off
experimental therapy with biological agents not expected to cause myelotoxicity
should have been off treatment for at least 3 weeks as wash-out period.

- Have had disease that has progressed within 6 months platinum-based chemotherapeutic

- Have no history of platinum allergy.

- Have a negative serum pregnancy test prior to the study entry and be practicing an
effective form of contraception if hysterectomy and/or oophorectomy were not part of
the prior treatment. It is expected that the overwhelming majority of ovarian cancer
patients would have had hysterectomy and oophorectomy as part of the original

- Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Have acceptable organ function, as evidenced by laboratory data:

- Aspartate aminotransferase and alanine aminotransferase less than 2.5 times
upper limit of normal (ULN)

- Direct bilirubin less than 1.5 times ULN

- Alkaline phosphatase less than 2.5 times ULN

- Absolute neutrophil count greater than or equal to 1500 cells/mm3

- White cell blood count greater than 3000cells/mm3

- Hemoglobin greater than or equal to 9.0 g/dL (can be post-transfusion)

- Platelets greater than 100,000/mm3 (can not be post-transfusion)

- Creatinine levels less than 1.5 times ULN

Exclusion Criteria:

- Not have participated in any clinical trial involving conventional or investigational
drugs or devices within the previous 3 weeks.

- Not have grade 2 or greater neuropathy.

- Have no additional active cancer in addition to the epithelial ovarian cancer within
the last 5 years, with the exception of superficial skin cancer (basal cell or
squamous cell skin carcinoma), carcinoma in situ of the cervix, Stage I endometrial
cancer with less than 50% invasion of the myometrium, or other adequately treated
Stage I or II cancer in complete remission.

- Be free of active infection requiring antibiotic treatment.

- Not have an additional uncontrolled serious medical condition or psychiatric illness.

- Not have an immune deficiency and be receiving combination anti-retroviral therapy

- Not have known brain metastases, as progressive neurologic dysfunction may develop,
that would confound the evaluation of neurologic and other adverse events.

- Absence of uncontrolled hypertension, arrhythmia, congestive heart failure or angina.
Patients who have had a myocardial infarction or cardiac surgery should be at lease 6
months from the event and free of active symptoms.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Description:

RECIST = Response Evaluation Criteria in Solid Tumors

Outcome Time Frame:

1 yr

Safety Issue:


Principal Investigator

Daniela Matei, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Indiana University


United States: Institutional Review Board

Study ID:

0704-07 IUCRO-0185



Start Date:

July 2007

Completion Date:

October 2013

Related Keywords:

  • Ovarian Cancer
  • recurrent ovarian cancer
  • platinum resistant
  • decitabine
  • Ovarian Neoplasms



Indiana University Cancer Center Indianapolis, Indiana  46202-5265