Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT03742245|
Recruitment Status : Not yet recruiting
First Posted : November 15, 2018
Last Update Posted : March 5, 2019
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Metastatic Breast Cancer||Drug: Olaparib Drug: Vorinostat||Phase 1|
This is a Phase I/Ib study testing the safety and preliminary efficacy of olaparib and vorinostat when used together in participants with relapsed/refractory and or metastatic breast cancer. Cancer cells grow in an uncontrolled manner and this causes damage to their DNA (genetic makeup). Cancer cells that cannot repair this damage will not survive and die. Unfortunately, cancer cells contain certain proteins whose job is to repair DNA damage. Poly (adenosine 5' diphosphoribose) polymerase (PARP) and histone deacetylase (HDAC) are two such proteins. Olaparib stops PARP from working, and vorinostat stops histone deacetylase from working. The use of olaparib and vorinostat together may better block the ability of cancer cells to repair their DNA damage. This may lead to even better killing of cancer cells.
The study will be done in two parts. In part one of the study, different dose levels of olaparib and vorinostat will be tested in several study participants. This part of the study will allow us to see the doses of olaparib and vorinostat that can be used safely together in participants with relapsed/refractory and/or metastatic breast cancer. Up to 4 different dose levels will be studied. In part two of the study, the dose level of olaparib and vorinostat found to be the safest in the first part of the study will be tested. This part of the study will allow us to see how well relapsed/refractory and/or metastatic breast cancer responds to treatment with olaparib and vorinostat. Participants who received the dose level of olaparib and vorinostat found to be the safest in the first part of the study will also take part in part two of the study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multicenter Phase I/Ib Trial of Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast Cancer|
|Estimated Study Start Date :||April 1, 2019|
|Estimated Primary Completion Date :||March 1, 2022|
|Estimated Study Completion Date :||September 1, 2022|
Experimental: Olaparib and Vorinostat
Phase I: Olaparib and vorinostat will be orally administered for 4 28-day cycles. Dose levels (DLs) are as follows: DL -1, 100 mg twice daily (b.i.d.) olaparib and 300 mg for 5 consecutive days per week vorinostat; DL 0 (starting dose), 200 mg twice daily (b.i.d.) olaparib and 300 mg once daily (q.d.) vorinostat; DL 1, 300 mg b.i.d. olaparib and 300 mg q.d. vorinostat; and DL 2, 300 mg b.i.d. olaparib and 400 mg q.d. vorinostat.
Phase Ib: Olaparib and vorinostat will be administered at the maximum tolerated dose (MTD) determined in the Phase I portion of the study for 4 28-day cycles. Participants who derive clinical benefit (complete response, partial response, or stable disease) after 4 cycles will continue to receive study treatment until unacceptable toxicity or disease progression.
- MTD [ Time Frame: 16 weeks ]Determine the MTD of the olaparib and vorinostat combination
- Dose-limiting toxicities (DLTs) and other adverse events [ Time Frame: 16 weeks ]Determine the DLTs and other adverse events associated with the olaparib and vorinostat combination, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v4.03
- Recommended Phase 2 dose (RP2D) [ Time Frame: 16 weeks ]Determine the RP2D of the olaparib and vorinostat combination
- Antitumor activity [ Time Frame: 16 weeks ]Assess the antitumor activity of the olaparib and vorinostat combination in an expansion cohort of patients with relapsed/refractory and/or metastatic breast cancer, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) 1:1
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03742245
|Contact: Houston Methodist Cancer Centerfirstname.lastname@example.org|
|Contact: Jenny Chang, M.D.||email@example.com|
|United States, Texas|
|Houston Methodist Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jenny Chang, M.D.||Houston Methodist Cancer Center|