Breast Cancer MetastaticPhase 1NCT03742245
Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast Cancer
A Phase 1 study testing Olaparib and Vorinostat in people with Breast Cancer Metastatic and Breast Cancer, run by The Methodist Hospital Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to test the safety and preliminary efficacy of olaparib and vorinostat when used together in participants with relapsed/refractory and or metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer Metastatic, Breast Cancer
- What is being tested?
- Olaparib and Vorinostat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jun 2019to 1 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of informed consent prior to any study-specific procedures.
- Female or male ≥18 years of age.
- Histologically or cytologically confirmed relapsed/refractory and/or metastatic breast cancer with the exception of human epidermal growth factor receptor 2-positive breast cancer.
- Evaluable or measurable disease as per the RECIST 1:1.
- Normal organ and bone marrow function measured within 28 days prior to administration of the study treatment.
- White blood cell (WBC) count >2,500/microL and <15,000/microL
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- Lymphocyte count ≥500/microL
- Total bilirubin (TBL) ≤1.5 × institutional ULN
- Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 × institutional ULN (patients with liver metastases ≤5 × ULN) and alkaline phosphatase (ALP) ≤2.5 × institutional ULN (patients with liver metastases ≤5 × ULN).
- Serum creatinine ≤1.5 × ULN and creatinine clearance (CrCl) estimated using the Cockcroft-Gault equation of ≥51 mL/min
- Eastern Cooperative Oncology Group performance status of 0 or 1.
- Life expectancy ≥6 months.
- Postmenopausal or evidence of non-childbearing status for women of childbearing potential (WOCBP): negative serum (beta-human chorionic gonadotropin) pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1.
- WOCBP must be willing to use 2 highly effective methods of contraception for the course of the study through 1 month after the last treatment dose.
- Male patients must be willing to use condom contraception for the course of the study through 3 months after the last treatment dose.
- Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- Willing to undergo biopsy as required by the study.
- Able to swallow pills and capsules
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation.
- Whole blood transfusions in the last 120 days prior to study entry.
- Unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study treatment.
- Concomitant use of known strong or moderate cytochrome P450 (CYP)3A inhibitors.
- Concomitant use of known strong or moderate CYP3A inducers.
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- Persistent toxicities (CTCAE Grade 2) caused by previous cancer therapy, excluding alopecia.
- Participants with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
- Known hypersensitivity to olaparib or vorinostat or any of their excipients or analogues (PARP/HDAC inhibitors).
- Breastfeeding women.
- No active malignancy except for non-melanoma skin cancer, in situ cervical cancer, or a treated cancer from which the patient has been continuously disease free for more than 5 years.
- Pneumonitis or at risk of pneumonitis.
- Uncontrolled brain or leptomeningeal metastases.
- Any systemic chemotherapy or radiation therapy within 4 weeks prior to study entry.
- Major surgery within 4 weeks of starting the study treatment.
- Participation in another clinical study with an investigational product during the last 3 months.
- Any previous treatment with PARP inhibitor including olaparib or HDAC inhibitor including vorinostat.
- New York Heart Association Class III or IV heart failure or unstable angina.
- History of liver disease, such as cirrhosis or active/chronic hepatitis B or C.
- Sustained or clinically significant cardiac arrhythmias including sustained ventricular tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced heart block (Mobitz II or higher atrioventricular nodal block), prolonged corrected QT interval (mean >470 milliseconds), or history of acute myocardial infarction.
- Risk factors for torsades de pointes such as hypokalemia, hypomagnesemia, cardiac failure, clinically significant/symptomatic bradycardia, or high-grade atrioventricular nodal block.
- Concomitant disease(s) that could prolong QT interval such as autonomic neuropathy (caused by diabetes or Parkinson's disease), human immunodeficiency virus (HIV), cirrhosis, uncontrolled hypothyroidism, or cardiac failure.
- Concomitant medication(s) known to prolong QT interval (patient must be off the drug for 2 weeks to be eligible).
- Presence of active or suspected acute or chronic uncontrolled infection or history of immunocompromise, including participants who are known to be serologically positive for HIV.
- Any severe and/or uncontrolled medical conditions or other conditions that could affect study participation, such as severely impaired lung function; any active (acute or chronic) or uncontrolled infection/disorders; or non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the study treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Houston Methodist Cancer Center
Houston, Texas, 77030
About this study
Official title: Multicenter Phase I/Ib Trial of Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast Cancer
The purpose of this study is to test the safety and preliminary efficacy of olaparib and vorinostat when used together in participants with relapsed/refractory and or metastatic breast cancer.
Read the detailed description
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.
- Conditions
- Breast Cancer Metastatic, Breast Cancer
- Being tested
- Olaparib, Vorinostat
- Keywords
- breast cancer, relapsed, refractory, metastatic
- Medical subject headings
- Breast Neoplasms, Recurrence, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OlaparibDrug
Also called AZD2281, KU-0059436, Lynparza
PARP inhibitor
VorinostatDrug
Also called Suberanilohydroxamic acid, Zolinza
HDAC inhibitor
| Study group | Role | What they receive |
|---|---|---|
| Olaparib and Vorinostat | Experimental | 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. . Patients who derive clinical benefit (CR, PR, or SD) after 4 cycles of treatment can continue to receive the study treatment until they experience unacceptable AEs or disease progression.
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. Receives: Drug: Olaparib; Drug: Vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD
Determine the MTD of the olaparib and vorinostat combination
Measured: 16 weeks
Secondary outcomes (3)
Dose-limiting toxicities (DLTs) and other adverse events
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
Measured: 16 weeks
Recommended Phase 2 dose (RP2D)
Determine the RP2D of the olaparib and vorinostat combination
Measured: 16 weeks
Antitumor activity
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
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2018
- Study start11 Jun 2019
- Primary completion1 Dec 2025
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, Polly A. Niravath, MD, The Methodist Hospital Research Institute
- Investigators
- Polly Niravath, M.D., Principal investigator, Houston Methodist Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03742245
- Sponsor's protocol ID
- Pro00020138
- Status last verified
- Mar 2026
- First submitted
- 12 Nov 2018
- Last updated
- 16 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Phase I/Ib Trial of Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT03742245
- Acronym / sponsor ID
- Pro00020138
- Conditions
- Breast Cancer Metastatic, Breast Cancer
- Keywords
- breast cancer, relapsed, refractory, metastatic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Collaborators
- AstraZeneca, Merck Sharp & Dohme LLC
- Study start
- 11 Jun 2019 (actual)
- Primary completion
- 1 Dec 2025 (actual)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 15 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test the safety and preliminary efficacy of olaparib and vorinostat when used together in participants with relapsed/refractory and or metastatic breast cancer.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Olaparib and Vorinostat | Experimental | Drug: Olaparib, Drug: VorinostatPhase 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. . Patients who derive clinical benefit (CR, PR, or SD) after 4 cycles of treatment can continue to receive the study treatment until they experience unacceptable AEs or disease progression. 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Provision of informed consent prior to any study-specific procedures.
- Female or male ≥18 years of age.
- Histologically or cytologically confirmed relapsed/refractory and/or metastatic breast cancer with the exception of human epidermal growth factor receptor 2-positive breast cancer.
- Evaluable or measurable disease as per the RECIST 1:1.
- Normal organ and bone marrow function measured within 28 days prior to administration of the study treatment.
Key exclusion criteria (25 listed)
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation.
- Whole blood transfusions in the last 120 days prior to study entry.
- Unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study treatment.
- Concomitant use of known strong or moderate cytochrome P450 (CYP)3A inhibitors.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OlaparibAlso: AZD2281, KU-0059436, LynparzaPARP inhibitor | Drug | Olaparib and Vorinostat |
| VorinostatAlso: Suberanilohydroxamic acid, ZolinzaHDAC inhibitor | Drug | Olaparib and Vorinostat |
Primary outcome
MTD
Time frame: 16 weeks
Determine the MTD of the olaparib and vorinostat combination
3 secondary outcomes
Dose-limiting toxicities (DLTs) and other adverse events
Time frame: 16 weeks
Recommended Phase 2 dose (RP2D)
Time frame: 16 weeks
Antitumor activity
Time frame: 16 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Polly Niravath, M.D. principal investigator
Houston Methodist Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Olaparib and Vorinostat in people with Breast Cancer Metastatic and Breast Cancer, run by The Methodist Hospital Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 16 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD (time frame: 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2026.