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

NCT03343054 | Completed Phase 1 Results

• 1 other identifier: C3441030
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 8

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.

Conditions

Neoplasms; Breast Neoplasms

Keywords

Phase 1; talazoparib; PF-06944076; MDV3800; BMN673; PARP inhibitor; Japanese; solid tumors; breast cancer; C3441030

Outcome Measures

Primary Outcomes (2)

• Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT)

  DLT was defined as any of the following adverse events occurred in 1st treatment cycle and attributable to talazoparib: hematologic- grade(G) 4 neutropenia greater than (\>)7days; Febrile neutropenia \>1 hour; G greater than or equal to (\>=)3 neutropenic infection, thrombocytopenia associated with G2 hemorrhage; G4 thrombocytopenia, anemia; G3 anemia required transfusion; daily dosing interrupted for \>=7 total days in first cycle for G3 neutropenia/thrombocytopenia. Non-hematologic: any G\>=3AE except non-clinically significant laboratory abnormalities, Non-hematologic AE deemed not clinically significant, nausea, vomiting, diarrhea responded to medical intervention within 72 hours, fatigue improved to G\>=2 within 7 days. Alanine/aspartate aminotransferase (ALT/AST)\>5\*upper limit of normal(ULN) and 2\*increases above baseline values; ALT/AST\>=3\*ULN concurrent with total bilirubin (TB)\>2\*ULN; TB\>5\*ULN; failure to deliver 75percent(%) of doses due to toxicities attributable to talazoparib.

  Cycle 1 (28 days)

• Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment

  Confirmed OR in participants was defined as the percentage of participants with complete response (CR) or partial response (PR) as best response determined by investigator as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)

Secondary Outcomes (35)

• Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

  From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)

• Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

  From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)

• Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03

  From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)

• Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry

  Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days

• Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology

  Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days

Study Arms (1)

talazoparib

EXPERIMENTAL

0.75 mg/day or 1.0 mg/day

Drug: talazoparib

Interventions

talazoparib DRUG

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

talazoparib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• \[Dose Expansion Part\]
• 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.
• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (8)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, 003-0804, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

Saitama Cancer Center

Kitaadachi-gun, Saitama, 362-0806, Japan

Location

National Cancer Center Hospital

Chuo-Ku, Tokyo, 104-0045, Japan

Location

Hakuaikai Medical Corporation Sagara Hospital

Kagoshima, 892-0833, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, 540-0006, Japan

Location

Related Publications (2)

• Kotani H, Masuda N, Yamashita T, Naito Y, Taira T, Inoue K, Takahashi M, Yonemori K, Toyoizumi S, Mori Y, Nagasawa T, Hori N, Iwata H. Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study. Breast Cancer. 2022 Nov;29(6):1088-1098. doi: 10.1007/s12282-022-01390-w. Epub 2022 Jul 30.

  PMID: 35907135 DERIVED

• Naito Y, Kuboki Y, Ikeda M, Harano K, Matsubara N, Toyoizumi S, Mori Y, Hori N, Nagasawa T, Kogawa T. Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study. Invest New Drugs. 2021 Dec;39(6):1568-1576. doi: 10.1007/s10637-021-01120-7. Epub 2021 Jun 23.

  PMID: 34160752 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Neoplasms; Breast Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2017
• First Posted: November 17, 2017
• Study Start: November 30, 2017
• Primary Completion: January 11, 2021
• Study Completion: July 18, 2024
• Last Updated: August 22, 2024
• Results First Posted: March 10, 2022

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (8)