A Phase 1 Dose-Escalation Trial of Talazoparib in Combination With Belinostat for Metastatic Breast Cancer, Metastatic Castration Resistant Prostate Cancer, and Metastatic Ovarian Cancer

University of Michigan Rogel Cancer Center1 site in 1 country26 target enrollmentMarch 4, 2021

InterventionsTalazoparib Belinostat

Overview

Phase: Phase 1
Intervention: Talazoparib
Conditions: Not specified
Sponsor: University of Michigan Rogel Cancer Center
Enrollment: 26
Locations: 1
Primary Endpoint: Dose limiting toxicities (DLT) within the first two cycles of treatment
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This Phase 1 dose-escalation trial is to determine the safety, tolerability and recommended phase 2 dose of talazoparib in combination with belinostat in subjects with Metastatic Breast Cancer, Metastatic Castration Resistant Prostate Cancer, and Metastatic Ovarian Cancer.

Registry

clinicaltrials.gov

Start Date

March 4, 2021

End Date

January 2, 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Michigan Rogel Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•One of the following disease types: Men or women with histologically confirmed metastatic or unresectable breast cancer that is HER2 negative as assessed by 2018 ASCO-CAP guidelines. Trial participants with hormone receptor positive disease must have progression on at least one hormonal therapy and a CDK inhibitor AND be considered a candidate for chemotherapy; OR, Men with metastatic castration resistant prostate cancer with progression on androgen deprivation therapy and at least one additional agent in the metastatic setting; OR, Women with metastatic high grade serous ovarian cancer with progression on at least one chemotherapy agent; OR, men or women with metastatic or unresectable pancreatic adenocarcinoma with progression on at least one chemotherapy regimen in the metastatic/unresectable setting
•Measurable disease as defined by RECIST 1.1 criteria.
•Trial participants must be at least 21 days from last dose of chemotherapy and recovered from all chemotherapy-related reversible toxicity to Grade 0 or 1, with the exception of alopecia and neuropathy.
•The last radiation therapy (including palliative radiation) must have occurred ≥3 weeks prior to study registration.
•Trial participants must have experienced disease progression at the time of study enrollment.
•ECOG performance status of 0 or
•Adequate organ and marrow function per protocol.
•Trial participants with treated brain metastases are eligible provided the metastases are recently treated and/or clinically stable and greater than 4 weeks has elapsed from time of treatment and date of initiation of study drug.
•Trial participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen should be included.
•Males and females of reproductive potential must use two forms of effective contraception during the duration of the trial and for minimum of 7 months after last dose of study drug. A woman of reproductive potential is defined as a premenopausal female with intact uterus and ovaries. For women, non-childbearing potential is defined as:

Exclusion Criteria

•Previous or current treatment with a histone deacetylase inhibitor (HDACi)S.
•Participation in other investigational studies concurrently if these therapies include a therapeutic intervention.
•Treatment with any investigational agent within 30 days (or 5 serum half-lives of the investigational drug, whichever is longer) of enrollment.
•Evidence of current serious uncontrolled concomitant cardiovascular nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (include uncontrolled diabetes mellitus) or gastrointestinal disease.
•History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to:
•Myocardial infarction or arterial thromboembolic events within 6 months prior to screening or severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease, or a QTc interval \> 450 msec.
•Uncontrolled hypertension or diabetes mellitus.
•Another known malignancy that is progressing or requires active treatment.
•Active infection requiring systemic therapy.
•Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

Arms & Interventions

Talozoparib in combination with Belinostat

Patients will receive Talozoparib in combination with Belinostat

Intervention: Talazoparib

Talozoparib in combination with Belinostat

Patients will receive Talozoparib in combination with Belinostat

Intervention: Belinostat

Outcomes

Primary Outcomes

Dose limiting toxicities (DLT) within the first two cycles of treatment

Time Frame: 10 weeks

Number of DLT's experienced by participants within the first two cycles. A DLT will be defined as any treatment related toxicity of grade 3 or 4 unless otherwise defined in the protocol. DLTs will be assessed via the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Secondary Outcomes

Plasma concentrations of talazoparib at steady state(Day 5 of cycle 1; up to day 5 of cycle 3)
Plasma concentrations of belinostat at steady state(Day 5 of cycle 1; up to day 5 of cycle 3)
Number of patients with an objective response(Up to 30 days post last treatment, up to approximately 6 months)
Proportion of patients experiencing toxicities. Participants may continue to receive the investigational study therapy until disease progression or unacceptable toxicity.(Up to 30 days post last treatment, up to approximately 6 months)