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

Primary Purpose

Metastatic Breast Cancer, Metastatic Castration-resistant Prostate Cancer, Metastatic Ovarian Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Talazoparib
Belinostat
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring PARP inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.
  • 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.

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.
  • 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.
  • Current or anticipated use within 7 days prior to enrollment, or anticipated use during the study, of strong P-gp inhibitors per protocol.
  • Subjects homozygous for UGT1A1*28 allele; this will be determined via clinical testing by polymerase chain reaction with capillary electrophoresis by the University of Michigan Molecular Diagnostics laboratory.
  • Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial.

Sites / Locations

  • University of Michigan Rogel Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Talozoparib in combination with Belinostat

Arm Description

Patients will receive Talozoparib in combination with Belinostat

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Proportion of patients experiencing toxicities. Participants may continue to receive the investigational study therapy until disease progression or unacceptable toxicity.
The proportion of patients experiencing toxicities will be reported by dose level and grade. Toxicities and grading per the NCI CTCAE version 5.0.
Plasma concentrations of talazoparib at steady state
Plasma concentrations of talazoparib at steady state will be measured to evaluate its pharmacokinetic (PK) profile, with combination therapy of talazoparib and belinostat. Sparse PK assessment will occur at multiple time points from day 5 of cycle 1 through day 5 of cycle 3 in order to assess steady-state trough levels. The plasma concentrations will be determined by liquid chromatography, high-resolution mass spectrometry, and summarized descriptively by dose level.
Plasma concentrations of belinostat at steady state
Plasma concentrations of belinostat at steady state will be measured to evaluate its PK profile, with combination of talazoparib and belinostat. Sparse PK assessment will occur at multiple time points from day 5 of cycle 1 through day 5 of cycle 3 in order to assess steady-state trough levels. The plasma concentrations will be determined by liquid chromatography, high-resolution mass spectrometry, and summarized descriptively by dose level.
Number of patients with an objective response
Number of patients with an objective response per the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 will be reported by dose level.

Full Information

First Posted
January 8, 2021
Last Updated
August 30, 2023
Sponsor
University of Michigan Rogel Cancer Center
Collaborators
Pfizer, Acrotech Biopharma Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04703920
Brief Title
Talazoparib in Combination With Belinostat for Metastatic Breast Cancer, Metastatic Castration Resistant Prostate Cancer, and Metastatic Ovarian Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 4, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
Collaborators
Pfizer, Acrotech Biopharma Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer, Metastatic Castration-resistant Prostate Cancer, Metastatic Ovarian Carcinoma
Keywords
PARP inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Talozoparib in combination with Belinostat
Arm Type
Experimental
Arm Description
Patients will receive Talozoparib in combination with Belinostat
Intervention Type
Drug
Intervention Name(s)
Talazoparib
Intervention Description
Talazoparib will be administered in increasing doses up to 1 mg orally once a day.
Intervention Type
Drug
Intervention Name(s)
Belinostat
Intervention Description
Belinostat will be administered in increasing doses up to 1000 mg/m2 IV once daily on days 1-5 of a 21-day cycle.
Primary Outcome Measure Information:
Title
Dose limiting toxicities (DLT) within the first two cycles of treatment
Description
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.
Time Frame
10 weeks
Secondary Outcome Measure Information:
Title
Proportion of patients experiencing toxicities. Participants may continue to receive the investigational study therapy until disease progression or unacceptable toxicity.
Description
The proportion of patients experiencing toxicities will be reported by dose level and grade. Toxicities and grading per the NCI CTCAE version 5.0.
Time Frame
Up to 30 days post last treatment, up to approximately 6 months
Title
Plasma concentrations of talazoparib at steady state
Description
Plasma concentrations of talazoparib at steady state will be measured to evaluate its pharmacokinetic (PK) profile, with combination therapy of talazoparib and belinostat. Sparse PK assessment will occur at multiple time points from day 5 of cycle 1 through day 5 of cycle 3 in order to assess steady-state trough levels. The plasma concentrations will be determined by liquid chromatography, high-resolution mass spectrometry, and summarized descriptively by dose level.
Time Frame
Day 5 of cycle 1; up to day 5 of cycle 3
Title
Plasma concentrations of belinostat at steady state
Description
Plasma concentrations of belinostat at steady state will be measured to evaluate its PK profile, with combination of talazoparib and belinostat. Sparse PK assessment will occur at multiple time points from day 5 of cycle 1 through day 5 of cycle 3 in order to assess steady-state trough levels. The plasma concentrations will be determined by liquid chromatography, high-resolution mass spectrometry, and summarized descriptively by dose level.
Time Frame
Day 5 of cycle 1; up to day 5 of cycle 3
Title
Number of patients with an objective response
Description
Number of patients with an objective response per the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 will be reported by dose level.
Time Frame
Up to 30 days post last treatment, up to approximately 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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. 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. 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. 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. Current or anticipated use within 7 days prior to enrollment, or anticipated use during the study, of strong P-gp inhibitors per protocol. Subjects homozygous for UGT1A1*28 allele; this will be determined via clinical testing by polymerase chain reaction with capillary electrophoresis by the University of Michigan Molecular Diagnostics laboratory. Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Monica Burness, M.D.
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Rogel Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cancer AnswerLine
Phone
800-865-1125
Email
CancerAnswerLine@med.umich.edu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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