RECRUITING

Olaparib in Combination with Vorinostat in Patients with Relapsed/Refractory And/or Metastatic Breast Cancer

Conditions

Breast Cancer Metastatic Breast Cancer relapsed refractory metastatic

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Multicenter Phase I/Ib Trial of Olaparib in Combination with Vorinostat in Patients with Relapsed/Refractory And/or Metastatic Breast Cancer

Quick Facts

Study Start:2019-06-11

Study Completion:2026-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03742245

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * 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	* 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. * 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.

Inclusion Criteria

Exclusion Criteria

* 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.
* 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

* 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.
* 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.

Contacts and Locations

Study Contact

Houston Methodist Cancer Center

CONTACT

713-441-0629

ccresearch@houstonmethodist.org

Jenny Chang, M.D.

CONTACT

713-441-0629

ccresearch@houstonmethodist.org

Principal Investigator

Jenny Chang, M.D.

PRINCIPAL_INVESTIGATOR

Houston Methodist Cancer Center

Study Locations (Sites)

Houston Methodist Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: The Methodist Hospital Research Institute

Jenny Chang, M.D., PRINCIPAL_INVESTIGATOR, Houston Methodist Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-06-11

Study Completion Date2026-03-01

Study Record Updates

Study Start Date2019-06-11

Study Completion Date2026-03-01

Terms related to this study

Keywords Provided by Researchers

breast cancer
relapsed
refractory
metastatic

Additional Relevant MeSH Terms

Breast Cancer Metastatic
Breast Cancer