Olaparib in Combination With Carboplatin for Refractory or Recurrent Women s Cancers

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT01237067
Phase
PHASE1
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 99 Years
Healthy Volunteers
Not accepted

Interventions

  • Carboplatin — DRUG
    A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of the trial will be AUC4. Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8. Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis.
  • Olaparib — DRUG
    A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of the trial will be AUC4. Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8. Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis.

Study Details

Background: \- Olaparib is an experimental anti-cancer drug that is part of a class of drugs called PARP inhibitors. PARP is a protein that is involved in repairing DNA damage, but it may also encourage precancerous cells to develop into cancer cells. Olaparib has been given safely in combination with carboplatin, a drug used to treat breast, ovarian, uterine, and cervical cancer, but more research is needed to determine whether the drugs are more effective when given together or which drug should be given first. Objectives: \- To determine the safety and effectiveness of combined carboplatin and olaparib as a treatment for gynecologic (female organ) or breast cancer. Eligibility: * Women at least 18 years of age who have breast, ovarian, uterine, or cervical cancer that has not responded to standard treatments. * Men at least 18 years of age who have metastatic breast cancer and have a BRCA-1/2 mutation. Design: * Participants will be screened with a physical examination and medical history, as well as blood and tumor samples and imaging studies as required by the researchers. Study participants will then be divided into two groups. * Group 1: Participants will receive olaparib tablets twice a day for 7 days (14 doses) and will receive carboplatin by vein on day 1 or 2, for a 21-day treatment cycle. Group 1 study is designed to determine the safety of new tablet formulation of olaparib. * Group 2: Participants will be divided into two smaller groups, with reversed treatment schedules. Group 2 study is designed to evaluate which drug should be given first through endpoint studies in blood samples. * Group 2A: Participants will receive olaparib tablets twice a day for 7 days (14 doses) and then carboplatin on day 8 of the first cycle. Cycle 2 will start with carboplatin on day 1 and olaparib starting on day 2 for 7 days (14 doses). * Group 2B: Participants will receive carboplatin on the first day of the first cycle, and then olaparib on day 2, twice a day for 7 days (14 doses) of the first cycle. Cycle 2 will start with 7 days of olaparib (14 doses) and carboplatin will be given on day 8. * From cycle 3 until completion of therapy, all Group 2 participants will follow the schedule used for Group 1 (carboplatin on day 1 or 2 of the week of olaparib therapy, also in 21-day cycles). * Additional blood and tissue samples and imaging studies will be conducted throughout the treatment period. * All participants may receive no more than 8 cycles of olaparib and carboplatin therapy, but may continue to take olaparib if their cancer responds to the treatment.

Key Dates

Start date
Feb 7, 2011
Status verified
Dec 2019
Primary completion
Nov 16, 2014
Completion
Dec 12, 2019

Study Design

Enrollment
77 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Group 1
    Dose esc: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of the trial will be AUC4. Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8. Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis
  • Experimental: Group 2A
    Randomized: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of the trial will be AUC4. Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8. Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis.
  • Experimental: Group 2B
    Randomized: A phase I 3 + 3 safety run-in will optimize tablet olaparib dose (d1-7) in combination with carboplatin on day 1. The carboplatin dose through the randomized portion of the trial will be AUC4. Subsequent accrual will randomize patients to one of 2 schedules on cycle 1 with the other schedule on cycle 2. A: olaparib d1-7 \> carbo d8; B: carbo d1 \> olaparib d2-8. Cycle 3-8 will be schedule B. After 8 cycles of carboplatin, olaparib will be administered alone on a daily basis.

Primary Outcome Measure

Determine the pharmacodynamic effects of the sequence of administration of olaparib and carboplatin and the schedule-associated safety of the combination. [ Time Frame: Cycle 1 at 24 and 48 hours ]

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical Center, 9000 Rockville PikeBethesdaMaryland20892-

Find similar trials in Bethesda, MD

By condition
Breast cancerEndometrial cancerOvarian cancer
By specialty
OncologyBreast oncologyWomen's healthGynecologic oncology
By research site
National Institutes of Health Clinical Center, 9000 Rockville Pike· Bethesda, MD

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