Talazoparib in Combination With Belinostat for Metastatic Breast Cancer, Metastatic Castration Resistant Prostate Cancer, and Metastatic Ovarian Cancer

NCT04703920 | Completed Phase 1 FDA Drug

• 2 other identifiers: UMCC 2020.122HUM00187603
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer; Metastatic Castration-resistant Prostate Cancer; Metastatic Ovarian Carcinoma; Metastic or Unresectable Pancreatic Adenocarcinoma

Keywords

PARP inhibitor

Outcome Measures

Primary Outcomes (1)

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

  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.

  10 weeks

Secondary Outcomes (4)

• 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

• 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

Study Arms (1)

Talozoparib in combination with Belinostat

EXPERIMENTAL

Patients will receive Talozoparib in combination with Belinostat

Drug: Talazoparib; Drug: Belinostat

Interventions

Talazoparib DRUG

Talazoparib will be administered in increasing doses up to 1 mg orally once a day.

Talozoparib in combination with Belinostat

Belinostat DRUG

Belinostat will be administered in increasing doses up to 1000 mg/m2 IV once daily on days 1-5 of a 21-day cycle.

Talozoparib in combination with Belinostat

Eligibility Criteria

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

You may qualify if:

• 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 1.
• 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:
• ≥45 years of age and has not had menses for \>2 years.
• Amenorrheic for \<2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation.
• Post hysterectomy, oophorectomy or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure.
• Ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• 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.
• Any contraindication to oral agents or significant nausea and vomiting, malabsorption, or significant small bowel resection that, in the opinion of the investigator, would preclude adequate absorption.
• Allergy to talazoparib, belinostat or to the inactive components of talazoparib or belinostat formulations.
• Pregnancy or breastfeeding.
• QTc ≥ 450 ms or congenital long QT syndrome given potential for prolongation with belinostat.
• Current or anticipated use within 7 days prior to enrollment, or anticipated use during the study of drugs which are moderate or strong inhibitors of UGT1A1 per protocol.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Pfizer: collaborator
• Acrotech Biopharma Inc.: collaborator

Study Sites (1)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms

Interventions

talazoparib; belinostat

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Monica Burness, M.D.

  University of Michigan Rogel 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: SPONSOR

Study Record Dates

• First Submitted: January 8, 2021
• First Posted: January 11, 2021
• Study Start: March 4, 2021
• Primary Completion: December 1, 2024
• Study Completion: January 2, 2025
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)