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

NCT ID: NCT05288127

Last Updated: 2022-03-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-08
• Study Completion Date: 2025-11-30

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.

Detailed Description

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. A total of 55 evaluable 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. As it may take several weeks to determine if a patient has experienced a response, a temporary pause in the accrual to the trial may be necessary to ensure that enrollment to the second stage is warranted.

The purpose of this study is to determine if Talzenna® can help breast cancer patients who have not inherited an altered BRCA gene. We have identified a genetic signature called HRD100 which identifies patients who may respond to Talzenna®.

Disease status will be followed by imaging studies at interval of every 12 weeks, until disease progression, start of non-study treatment, withdrawal of consent to study participation, death or end of the study. RECIST 1.1 will be used as the primary endpoint of the response rate. Safety will be monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Appendix 2).

Study Treatment will continue until any of the following occurs:

1. Disease progression, as defined by Response Evaluation Criteria in Solid Tumour (RECIST version 1.1);

2. Unacceptable toxicity;

3. Intercurrent illness that necessitates discontinuation of study treatment;

4. Investigator's decision to withdraw the subject,

5. Pregnancy;

6. Major violation to study treatment or procedure requirements;

7. Withdrawal of consent to treatment;

8. Death;

9. End of the study;

10. Other administrative reasons requiring cessation of study treatment.

Specific procedures to be performed during the trial, as well as their prescribed times and associated visit windows, are outlined in the SCHEDULE OF ACTIVITIES (SoA).

The study will be conducted in conformance with Good Clinical Practices.

The primary objective of the trial is to determine the objective response rate (CR+PR) of the single agent talazoparib in metastatic TNBC patients with enriched HRD signature using RECIST 1.1. Secondary Objective is to determine the progression free survival (PFS) and overall survival (OS) of talazoparib in metastatic TNBC patients.

Exploratory Objectives is to evaluate the HRD signature(s) in predicting response to PARP inhibitor in metastatic TNBC patients.

Conditions

HRD 100 Gene Expression High; Triple Negative Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Talazoparib Single Agent

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.

Group Type: EXPERIMENTAL

Talazoparib

Intervention Type: 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.

Interventions

Talazoparib

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated informed consent form.

2. 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.

3. Women, aged 18 and above.

4. Received either one or two prior systemic treatments for metastatic breast cancer.

5. Histologically confirmed metastatic or recurrent triple-negative breast cancer (defined as ER <1%, PR <1%, HER2 negative, as per ASCO CAP guidelines).

6. Documented disease progression on the most recent therapy.

7. Have availability of 10 ml blood for germline BRCA testing if previous record of germline BRCA mutation status is not available.

8. 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.

9. 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.

10. Can provide one 10ml and one 6-ml blood samples for future biomedical research.

11. Has classification as HRD High based on the HRD 100 gene expression analysis (Appendix 4)

12. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix 1).

13. 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
• Hemoglobin ≥ 9.0 g/dL with last transfusion at least 14 days before randomization
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3

14. Females of childbearing potential must be willing to use adequate contraception for the course of the study through at least 7 months after the last dose of study drug.

15. Patient must be able to swallow pills.

6. 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

7. 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.

8. 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.

9. Has a known history of Human Immunodeficiency Virus (HIV).

10. Has known active Hepatitis B or Hepatitis C.

11. Has an active infection requiring systemic therapy.

12. Has significant cardiovascular disease, such as: History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months;

13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.

14. 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.

15. Has a known hypersensitivity to the components of the study drug or its analogs.

16. Known active brain metastases and/or carcinomatous meningitis.

Exclusion Criteria

1. Has ER-positive or PR-positive breast cancer.

2. Has HER2-positive breast cancer.

3. Have received prior treatment with a PARP inhibitor

4. Is currently on strong P-glycoprotein inhibitors.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Cancer Research Malaysia

OTHER

Sponsor Role: collaborator

Pfizer

INDUSTRY

Sponsor Role: collaborator

Pantai Hospital Kuala Lumpur

UNKNOWN

Sponsor Role: collaborator

Hospital Sultan Ismail

UNKNOWN

Sponsor Role: collaborator

University of Malaya

OTHER

Sponsor Role: lead

Responsible Party

Ho Gwo Fuang

Professor Dr Ho Gwo Fuang

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gwo Fuang Ho, FRCR

Role: PRINCIPAL_INVESTIGATOR

University of Malaya

Locations

University Malaya Medical Centre

Kuala Lumpur, Kuala Lumpur, Malaysia

Site Status: RECRUITING

Countries

Malaysia

Central Contacts

Gwo Fuang Ho, FRCR

Role: CONTACT

gwofuang@gmail.com

0379492120 ext. 2120

Wei Ying Chye

Role: CONTACT

wychye@gmail.com

0379492120 ext. 2120

Facility Contacts

Wei Ying Chye

Role: primary

wychye@gmail.com

0379492120 ext. 2120

Other Identifiers

IIT-CRM2020001

Identifier Type: -

Identifier Source: org_study_id