Talazoparib Maintenance Therapy in Triple-negative Breast Cancer

TNBC - Triple-Negative Breast Cancer Clinical Trial

Official title: A Randomized Phase II Clinical Trial of Talazoparib Maintenance Therapy in Triple-negative Breast Cancer Patients Who Showed Platinum-sensitivity on First- or Second-line Platinum-based Chemotherapy

Status Not yet recruiting

Clinical Trial Summary

The investigators propose a randomized phase II clinical trial of talazoparib maintenance therapy in TNBC patients whose tumor showed clinical benefit (platinum-sensitivity) to first- or second-line platinum-based chemotherapy (monotherapy or combination with other agents).

Patients are eligible when they meet at least one of two following platinum-sensitivity criteria:

1. They should have received 6 tri-weekly doses or 18 weekly doses of platinum-based therapy in non-progression status (at least stable disease) at the time of enrollment;

2. They should remain in complete or partial response status after 4-6 tri-weekly doses or 12-18 weekly doses of platinum-based chemotherapy. Eligible patients are enrolled to the trial within 4 to 8 weeks after last chemotherapy and 1:1 randomized to receive talazoparib versus placebo maintenance therapy.

The primary endpoint is PFS by RECIST 1.1 after randomization. The secondary endpoints include OS, time from randomization to second progression or death (PFS2), and objective response rate (ORR) by RECIST 1.1, adverse events by CTCAE 5.0 criteria, quality of life evaluated by EORTC-QLQ-C30, and EuroQoL EQ-5D.

Clinical Trial Description

Randomized double-blind placebo controlled phase II trial

This is a double-blind, placebo-controlled randomized phase II study, and the TNBC patients showing platinum-sensitivity after first- or second-line platinum-based chemotherapy will be screened. The total doses of platinum-based chemotherapy will be 4 or 6 doses for tri-weekly regimens and 12 or 18 doses for weekly regimen before randomization

. The platinum sensitivity is determined as follows,

1. Remaining stable disease after 6 tri-weekly doses or 18 weekly doses of platinum-based therapy (stable disease after 6 cycles)

2. Remaining complete or partial response status after 4-6 tri-weekly doses or 12-18 weekly doses of platinum-based chemotherapy (partial or complete response after 4-6 cycles)

The platinum sensitivity of the patients will be determined before enrollment to the clinical trial by review of central investigation institution (Yonsei Cancer Center) based on the the image reading results and, if necessary, the raw imaging data to determine that there is no tumor progression, tumor size increase, or new lesions.

The platinum-based chemotherapy can be either monotherapy or combination doublet chemotherapy of carboplatin or cisplatin with following combination partners: Paclitaxel, Docetaxel, Gemcitabine, Eribulin, Vinorelbine, Capecitabine, and Nab-paclitaxel. The combined targeted therapy agents including bevacizumab will be allowed but should be discontinued before randomization.

The patient with any BRCA1/2 mutation status is eligible. Germline BRCA1/2 test will be performed with reimbursement from South Korean health insurance in the study subject, if the subjects are under the age of 60 or have family history of BRCA-related cancers before enrollment. The testing results will be verified by the investigator. If the germline BRCA1/2 test is not covered by national health insurance (patients over 60 years of age and no family history), the BRCA1/2 germline testing will be performed with study support.

The germline BRCA mutation status will be determined before randomization if the patient do not have BRCA mutation results before. The eligible patients will be assigned to each treatment arm after 1:1 randomization. The patients will be stratified on randomization with following factors.

1. 1st line platinum-based chemotherapy versus 2nd line platinum-based chemotherapy*

2. Response (CR/PR vs. stable disease) to the prior platinum-based chemotherapy

3. BRCA status: wild-type (including benign variants and variants of unknown significance) versus BRCA1/2-mutated (pathogenic mutation)

• For the patient who recurred within 12 months after the last dose of (neo)adjuvant chemotherapy for operable stage breast cancer, the (neo)adjuvant chemotherapy will be considered as one line of chemotherapy.

The Arm A (Experimental arm) Maintenance therapy with talazoparib (1mg once daily) (once daily 1.0 mg oral administration), 103patients The Arm B (Control arm) Maintenance therapy with placebo (once daily 1.0 mg oral administration), 103patients

The maintenance talazoparib will be initiated 4 to 8 weeks after the last dose of platinum-based chemotherapy. The talazoparib treatment will continue until disease progression by RECIST 1.1, unacceptable toxicity, or death.

Computed tomography or magnetic resonance imaging of the chest, abdomen, and pelvis will be performed at baseline, and every 8 weeks until disease progression after then. ;

Related Conditions & MeSH terms

• Breast Neoplasms
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Neoplasms

• NCT number: NCT04755868
• Study type: Interventional
• Source: Yonsei University
• Contact: Joohyuk sohn
• Phone: +82-2-2228-8135
• Email: oncosohn@yuhs.ac
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 2021
• Completion date: March 1, 2024