Efficacy of Talazoparib in Asian Metastatic Breast Cancer Patients With a Homologous Recombinant Deficiency (HRD) Signature

NCT05288127 | Unknown Phase 2

• 1 other identifier: IIT-CRM2020001
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, non randomised, investigator-initiated Phase II study of single agent talazoparib (Talzenna®) in metastatic triple negative breast cancer patients with enriched HRD signature. Approximately 55 subjects will be enrolled in this study to examine the efficacy of talazoparib when given orally 1mg daily for days 1 to 28 for up to 28 months. The study will be conducted using the Simon two-stage phase II design, whereby this study will initially enroll 19 patients with RECIST v1.1 measurable disease with enriched HRD signature (stage I). There will be one interim analysis at the end of stage I and if 3 of the 19 have a response, then no further patient will be accrued. If 4 or more of the 19 patients have a response, then accrual would continue to stage II until a total of 55 patients have been enrolled. This study will be conducted in conformance with Good Clinical Practices. Specific procedures to be performed during the trial, as well as their prescribed times and associated visit windows, are outlined in the Trial Flow Chart.

Conditions

HRD 100 Gene Expression High; Triple Negative Breast Cancer

Keywords

Talazoparib; HRD 100 gene; Triple Negative Breast Cancer; BRCA 1/2

Outcome Measures

Primary Outcomes (1)

• Overall Responsive Rate (ORR) as assessed in RECIST 1.1

  It is commonly used in clinical trials to evaluate cancer treatments for objective response in solid tumors. The observed effect is attributable directly to the drug, not the natural history of the disease. Its application in tumor progression measurement is well accepted by regulatory authorities.

  [Time Frame: up to 28 months]

Secondary Outcomes (2)

• Progression-free Survival (PFS) using Kaplan-Meier (KM) method

  [Time Frame: up to 28 months]

• Overall Survival (OS) using Kaplan-Meier (KM) method

  [Time Frame: up to 28 months]

Study Arms (1)

Talazoparib Single Agent

EXPERIMENTAL

The study will have 1 treatment group. Patients will receive a single oral dose of talazoparib (Talzenna®) 1mg/day daily for 28-day cycles until progressive disease, limiting toxicities, intercurrent medical issues, patient withdrawal of consent, death, or end of trial whichever occurs first. Treatment will be administered on an outpatient basis. Talazoparib should be taken orally once daily (i.e., continuous daily dosing) at approximately the same time each day (preferably in the morning). Talazoparib will be swallowed whole and may be taken with or without food. If a subject vomits a dose, the subject should not take a second dose that calendar day. The subject should resume daily dosing the next day. Daily dosing of talazoparib can be interrupted for recovery from toxicity for up to 28 days. For interruptions longer than 28 days, treatment at the same or a reduced dose can be considered if the evidence of response or clinical benefit to talazoparib is noted.

Drug: Talazoparib

Interventions

Talazoparib DRUG

The recommended dose is 1 mg talazoparib once daily. Patients should be treated until disease progression or unacceptable toxicity occurs. Daily dosing of talazoparib can be interrupted for recovery from toxicity for up to 28 days. For interruptions longer than 28 days, treatment at the same or a reduced dose can be considered based on the if evidence of response or clinical benefit to talazoparib is noted. Missing dose If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time. Dose adjustments: To manage adverse drug reactions, interruption of treatment or dose reduction based on severity and clinical presentation should be considered.

Talazoparib Single Agent

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Participant eligibility is based on gender identity.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form.
• Stated willingness to comply with all study procedures (including if needed to undergo germline BRCA testing and counselling as per local hospital practice) and availability for the duration of the study.
• Women, aged 18 and above.
• Received either one or two prior systemic treatments for metastatic breast cancer.
• Histologically confirmed metastatic or recurrent triple-negative breast cancer (defined as ER \<1%, PR \<1%, HER2 negative, as per ASCO CAP guidelines).
• Documented disease progression on the most recent therapy.
• Have availability of 10 ml blood for germline BRCA testing if previous record of germline BRCA mutation status is not available.
• If germline BRCA 1 or 2 (1/2) mutation positive, should be among the 5 patients (in Stage I) or 9 patients (in Stage II) with germline BRCA 1/2 mutation positive.
• Can provide archival tumor tissue sample. Note: Formalin-fixed, paraffin embedded (FFPE) tissue blocks or tissues sections (\>30% neoplastic cells, 2 x 10µm tissue curls each in 2 sterile 1.5ml-micro-centrifuge tubes) and 10 unstained slides are needed.
• Can provide one 10ml and one 6-ml blood samples for future biomedical research.
• Has classification as HRD High based on the HRD 100 gene expression analysis (Appendix 4)
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1).
• Has adequate organ function as defined below: • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ×upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT ≤ 5 × ULN
• Total serum bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for Gilbert's syndrome)
• Calculated creatinine clearance ≥ 30 mL/min by local laboratory or Cockcroft-Gault formula

You may not qualify if:

• Has ER-positive or PR-positive breast cancer.
• Has HER2-positive breast cancer.
• Have received prior treatment with a PARP inhibitor
• Is currently on strong P-glycoprotein inhibitors.
• Has other malignancy that is either active or for which patients have received treatment within the last 5 years excluding non-melanoma skin cancer and carcinoma in situ of cervix
• Have received platinum may not have relapsed within 6 months of the last dose of prior platinum therapy. For patients who have received platinum, at least 6 months must have elapsed between the last dose of platinum-based treatment and enrollment.
• Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
• Has a known history of Human Immunodeficiency Virus (HIV).
• Has known active Hepatitis B or Hepatitis C.
• Has an active infection requiring systemic therapy.
• Has significant cardiovascular disease, such as: History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months;
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through at least 7 months after the last dose of study drug.
• Has a known hypersensitivity to the components of the study drug or its analogs.
• Known active brain metastases and/or carcinomatous meningitis.

Sponsors & Collaborators

• University of Malaya: lead
• Cancer Research Malaysia: collaborator
• Pfizer: collaborator
• Pantai Hospital Kuala Lumpur: collaborator
• Hospital Sultan Ismail: collaborator

Study Sites (1)

University Malaya Medical Centre

Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

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

Study Officials

• Gwo Fuang Ho, FRCR

  University of Malaya

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gwo Fuang Ho, FRCR

CONTACT

0379492120; gwofuang@gmail.com

Wei Ying Chye

CONTACT

0379492120; wychye@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Dr Ho Gwo Fuang

Study Record Dates

• First Submitted: January 27, 2022
• First Posted: March 21, 2022
• Study Start: March 8, 2022
• Primary Completion: June 1, 2024
• Study Completion: November 1, 2025
• Last Updated: March 21, 2022

Record last verified: 2022-03

Locations

MY (1)