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

Completed · Phase 1

Conditions studied: Ovarian Cancer, Breast Cancer, Primary Peritoneal Cancer, Fallopian Tube Cancer, Endometrial Cancer

In brief

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 facts

Study ID

NCT01237067

Run by

National Cancer Institute (NCI)

People needed

77

Starts

2011-02-07

Expected to finish

2019-12-12

Last updated by the study team

2019-12-17

Who can join

Age: 18 and older, up to 99. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Patients who have had treatment for their disease, such as chemotherapy, biological therapy, radiotherapy, surgery, or complementary and alternative therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study.
• Patients who were treated with other PARP inhibitors greater than 28 days prior to study are eligible.
• Must be at least 2 weeks from the last phase 0 intervention (longer at the discretion of the PI) and at least 1 day from non-cancer-related complementary and alternative medicine prior to entering the study.
• Previous treatment with olaparib (AZD2281).
• Invasive cancer, other than co-existent breast/gynecologic cancers, within the past 2 years. Noninvasive nonmelanoma skin cancers are not exclusions.
• Patients with known brain metastases diagnosed within 1 year will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Patients with brain metastases diagnosed greater than 1 year prior to study entry may be considered if they received sterilizing therapy to the CNS (resection or radiation) and have been CNS recurrence-free for a full 1-year period
• History of grade 4 allergic reactions to platinums:
• Patients with allergic reaction to platinums (up to and including grade 3 without a reaction protocol, and up to and including grade 2 in the face of aggressive pre-treatment) may be eligible pending review of experience, and PI approval.
• Patients who have not been rechallenged after a severe reaction may be eligible on a case-by-case basis.
• Clinically significant GI bleeding or hemoptysis within 28 days prior to the start of the study
• Inability to swallow pills
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (no antibiotics prior to entering the study within 7 days), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and breast-feeding women: If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately.
• HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2281. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy such as carboplatin. HIV- positive patients who are not on combination antiretroviral therapy but with CD4 counts >500, eligibility is a PI decision on an individual patient basis.
• Major surgery within the past 28 days

Where it is running

• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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