A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT03343054
• Recruitment Status: Active, not recruiting
• First Posted: November 17, 2017
• Last Update Posted: February 10, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: November 11, 2017
• First Posted Date: November 17, 2017
• Last Update Posted Date: February 10, 2021
• Actual Study Start Date: November 30, 2017
• Actual Primary Completion Date: January 11, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 5, 2019)

• Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: Baseline up to 28 days ]
  Number of participants with Dose-limiting toxicities (DLT)
• Number of Participants With Objective Response [ Time Frame: Baseline up to disease progression or any case of death ]
  OR is defined as a complete response (CR) or partial response (PR) according to RECIST v.1.1. recorded from baseline until disease progression or death due to any cause.

Original Primary Outcome Measures (submitted: November 11, 2017)

Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: Baseline up to 28 days ]

Number of participants with Dose-limiting toxicities (DLT)

Current Secondary Outcome Measures (submitted: April 5, 2019)

• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, hours post-dose ]
  Maximum Observed Plasma Concentration (Cmax)
• Area under the Concentration-Time Curve (AUC) [ Time Frame: 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 168 hours post-dose ]
  AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
• Plasma Decay Half-Life (t1/2) [ Time Frame: 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 168 hours post-dose ]
  Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 168 hours post-dose ]
  Time to Reach Maximum Observed Plasma Concentration (Tmax)
• Objective Response - Number of Participants With Objective Response [ Time Frame: Baseline up to 12 months ]
  OR is defined as a complete response (CR) or partial response (PR) according to RECIST v.1.1. recorded from baseline until disease progression or death due to any cause.
• Pre-dose Plasma Concentration (Ctrough) [ Time Frame: 0 (pre-dose) on Day 1 of Cycle 2, 3 and 4 ]
  Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.
• Time to tumor Response (TTR) [ Time Frame: From initiation of treatment up to initial objective response ]
  TTR is defined as the time from the first dose date to date of first documentation of OR.
• Disease Control (DC) [ Time Frame: Baseline up to disease progression or any case of death ]
  DC is defined as CR, PR or SD according to the RECIST version 1.1 recorded in the time period between first dose of study treatment and disease progression or death to any cause.
• Progression Free Survival (PFS) [ Time Frame: Baseline up to disease progression or any cause of death ]
  PFS is defined as the time from the first dose date to date of first documentation of PD or death due to any cause.
• Overall Survival (OS) [ Time Frame: Baseline up to any cause of death ]
  OS is defined as the time from the first dose date to date of death due to any cause

Original Secondary Outcome Measures (submitted: November 11, 2017)

• Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, hours post-dose ]
  Maximum Observed Plasma Concentration (Cmax)
• Area under the Concentration-Time Curve (AUC) [ Time Frame: 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 168 hours post-dose ]
  AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
• Plasma Decay Half-Life (t1/2) [ Time Frame: 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 168 hours post-dose ]
  Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
• Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 0, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 168 hours post-dose ]
  Time to Reach Maximum Observed Plasma Concentration (Tmax)
• Objective Response - Number of Participants With Objective Response [ Time Frame: Baseline up to 12 months ]
  OR is defined as a complete response (CR) or partial response (PR) according to RECIST v.1.1. recorded from baseline until disease progression or death due to any cause.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors
• Official Title: A PHASE 1 STUDY OF THE SAFETY, PHARMACOKINETICS AND ANTI-TUMOR ACTIVITY OF TALAZOPARIB, POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITOR, IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS

Brief Summary

This is a Phase 1 study which consists of 2 parts; Dose Escalation part and Expansion part.

The dose escalation part is open-label, and evaluates safety, preliminary efficacy and PK of single-agent talazoparib in sequential cohorts of adult patients with advanced solid tumors who are resistant to standard therapy or for whom no standard therapy is available.

In the dose escalation part, up to 18 (minimum 3) patients are expected to be enrolled depending on the observed DLTs.

The expansion part is designed to assess the efficacy, safety and PK of single-agent talazoparib at RP2D determined in the dose escalation part in adult patients with locally advanced or metastatic breast cancer who have deleterious or suspected deleterious germline BRCA1 or BRCA2 mutations.

In the expansion part, a minimum of 17 patients will be enrolled evaluable for the primary endpoint.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Neoplasms
• Breast Neoplasms

Intervention

Drug: talazoparib

Talazoparib will be administered orally on a continuous basis. Talazoparib may be taken with or without food. Each cycle will consist of 28 days.

Study Arms

Experimental: talazoparib

0.75 mg/day or 1.0 mg/day

Intervention: Drug: talazoparib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 8, 2021): 28
• Original Estimated Enrollment (submitted: November 11, 2017): 18
• Estimated Study Completion Date: July 1, 2022
• Actual Primary Completion Date: January 11, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

[Dose Escalation Part]

Inclusion Criteria:

• Histological or cytological diagnosis of locally advanced or metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
• ECOG Performance Status 0 or 1.
• Adequate Bone Marrow, Renal and Liver Function.

Exclusion Criteria:

• Patients with known symptomatic brain metastases requiring steroids.
• Current use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP within 1 week or 5 half lives which ever is longer prior to the first dose of study treatment.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception.

[Dose Expansion Part]

Inclusion Criteria:

• Histologically or cytologically confirmed carcinoma of the breast.
• Locally advanced breast cancer that is not amenable to curative radiation or surgery and/or metastatic disease.
• Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or BRCA2 mutation by Myriad Genetics' BRACAnalysis CDx test.
• No more than 3 prior chemotherapy-inclusive regimens for locally advanced or metastatic disease.
• Have measurable lesion by the RECIST v.1.1.
• ECOG Performance Status 0-2.
• Adequate Bone Marrow, Renal and Liver Function.

Exclusion Criteria:

• First-line locally advanced or metastatic breast cancer with no prior neoadjuvant and adjuvant chemotherapy.
• Prior treatment with a PARP inhibitor.
• Objective disease progression while receiving platinum chemotherapy administered for locally advanced or metastatic disease.
• HER2 positive breast cancer.
• Active inflammatory breast cancer.
• Central nervous system (CNS) metastases.
• Current or anticipated use within 7 days prior to the first dose of study treatment, or anticipated use during the study of strong P-gp inhibitors.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT03343054
• Other Study ID Numbers: C3441030
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: February 2021