A Study Evaluating Talazoparib in Relapsed Ovarian, Fallopian Tube, and Peritoneal Cancer

A Phase 2, Multiple-Cohort, Open-Label, International Study of Talazoparib Monotherapy and Talazoparib Plus Temozolomide in Women With Relapsed Ovarian, Fallopian Tube, and Peritoneal Cancer

The purpose of this phase 2, multiple-cohort, randomized, open-label, international study of talazoparib (a poly (ADP-ribose) polymerase (PARP) inhibitor) is to compare the efficacy and safety of talazoparib monotherapy and talazoparib plus temozolomide in women with relapsed ovarian, fallopian tube, and peritoneal cancer.

Study Overview

• Status: Withdrawn
• Conditions: Ovarian Cancer
• Intervention / Treatment: Drug: Talazoparib; Drug: Temozolomide

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women ≥ 18 years of age and willing and able to provide informed consent
• Relapsed, histologically confirmed ovarian, fallopian tube, and peritoneal cancer. Histologic subtypes include serous, endometrioid, clear-cell, mixed, undifferentiated histology, and carcinosarcoma.
• Sufficient archival tumor tissue available or consent to a fresh tissue biopsy for biomarker analysis. Consent to blood sample collection for biomarker analysis is required.
• Disease progression per RECIST 1.1 during or after the last treatment. Have metastatic disease with at least 1 target tumor lesion measurable per RECIST 1.1 on the screening scan. Lesions used for biopsies cannot be designated as a measurable lesion for RECIST 1.1 assessments.
• Additional criteria for cohort 1 include the following:
• Have a deleterious germline or a somatic BRCA1 or BRCA2 mutation, or a high diagnostic HRD test score (myChoice score ≥ 42), which represents a loss of DNA repair function based on testing performed at a sponsor-approved laboratory
• Received at least 1 and no more than 3 platinum-based chemotherapy regimens (prior bevacizumab is allowed) and the last dose is ≥ 28 days before randomization
• No prior PARP inhibitor treatment (COHORT 1 ONLY)
• Additional criteria for cohorts 2 and 3 include the following:
• Received at least 2 platinum-based chemotherapy regimens (including first-line chemotherapy; prior bevacizumab is allowed) and the last dose is ≥ 28 days before randomization
• Received prior PARP inhibitor treatment as a single agent or in combination therapy regimen and the last dose is ≥ 28 days before randomization, as follows:
• For cohort 2 only: Received PARP inhibitor treatment for ≥ 6 months and had a response of CR, PR, or stable disease for ≥ 6 months
• For cohort 3 only: Received PARP inhibitor treatment for < 6 months with no response (disease progression or stable disease)
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Estimated life expectancy of ≥ 3 months.
• Able to swallow drugs, have no known intolerance to study drugs or excipients, and able to comply with study requirements.

Exclusion Criteria:

• Have not recovered (recovery is defined as National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] grade ≤ 1) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting eligibility requirements.
• Use of any investigational agent within 14 days before randomization.
• Had > 2 paracentesis procedures within 28 days before randomization.
• Major surgery within 14 days before randomization.
• Requirement for intravenous alimentation (at the time of randomization).
• Diagnosis of MDS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: talazoparib; Cohorts 1A (PARP inhibitor naïve), 2A (PARP inhibitor sensitive), and 3A (PARP inhibitor refractory)	Drug: Talazoparib; Talazoparib monotherapy 1mg/day orally; Other Names: MDV3800; BMN673
ACTIVE_COMPARATOR: talazoparib + temozolomide; Cohorts 1B (PARP inhibitor naïve), 2B (PARP inhibitor sensitive), and 3B (PARP inhibitor refractory)	Drug: Talazoparib; Talazoparib monotherapy 1mg/day orally; Other Names: MDV3800; BMN673; Drug: Temozolomide; temozolomide 37.5 mg/m2 on days 1-5 of each cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine Objective Response Rate (ORR)	Anticipated in about 44 months following first patient enrolled

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS)	Anticipated in about 44 months following first patient enrolled
PFS at 24 weeks	Anticipated in about 44 months following first patient enrolled
Gynecologic Cancer Intergroup (GCIG) CA125 response rate	Anticipated in about 44 months following first patient enrolled
Clinical benefit rate at 24 weeks	Anticipated in about 44 months following first patient enrolled
Duration of response (DOR)	Anticipated in about 44 months following first patient enrolled
Time to response	Anticipated in about 44 months following first patient enrolled
Overall survival	Anticipated in about 44 months following first patient enrolled
Safety as assessed by percentage of patients with any Adverse Event (AE), AE leading to Study Drug Discontinuation, AE leading to death, SAE, AE related to study drug, SAE related to study drug.	Anticipated in about 44 months following first patient enrolled
Pharmacokinetics of talazoparib as assessed by trough plasma concentrations	Anticipated in about 44 months following first patient enrolled

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Medivation, Inc.; Myriad Genetic Laboratories, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (ANTICIPATED): June 1, 2020

Study Registration Dates

• First Submitted: July 14, 2016
• First Submitted That Met QC Criteria: July 14, 2016
• First Posted (ESTIMATE): July 18, 2016

Study Record Updates

• Last Update Posted (ACTUAL): September 18, 2018
• Last Update Submitted That Met QC Criteria: September 14, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Poly(ADP-ribose) Polymerase Inhibitors; Temozolomide; Talazoparib
• Other Study ID Numbers: MDV3800-11