Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast Cancer

NCT03742245 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro00020138
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer Metastatic; Breast Cancer

Keywords

breast cancer; relapsed; refractory; metastatic

Outcome Measures

Primary Outcomes (1)

• MTD

  Determine the MTD of the olaparib and vorinostat combination

  16 weeks

Secondary Outcomes (3)

• Dose-limiting toxicities (DLTs) and other adverse events

  16 weeks

• Recommended Phase 2 dose (RP2D)

  16 weeks

• Antitumor activity

  16 weeks

Study Arms (1)

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.

Drug: Olaparib; Drug: Vorinostat

Interventions

Olaparib DRUG

PARP inhibitor

Also known as: AZD2281, KU-0059436, Lynparza

Olaparib and Vorinostat

Vorinostat DRUG

HDAC inhibitor

Also known as: Suberanilohydroxamic acid, Zolinza

Olaparib and Vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AstraZeneca: collaborator
• The Methodist Hospital Research Institute: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Houston Methodist Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Recurrence; Neoplasm Metastasis

Interventions

olaparib; Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Polly Niravath, M.D.

  Houston Methodist Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Section Chief, Breast Oncology

Study Record Dates

• First Submitted: November 12, 2018
• First Posted: November 15, 2018
• Study Start: June 11, 2019
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (1)