FUnctional Selection of Advanced Breast Cancer Patients for Talazoparib Treatment Using the REpair Capacity (RECAP) Test

NCT06193525 | Recruiting Phase 2

• 2 other identifiers: MEC 19-00702018-002914-10
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to prove that the RECAP test is capable of selecting advanced breast cancer patients sensitive for treatment with the PARP inhibitor talazoparib. Participants will undergo an ultrasound-guided biopsy and a blood withdrawal. Homologous Recombination (HR) deficient patients (approximately 30%) can start talazoparib treatment until progression of the disease or unacceptable side-effects and their response will be evaluated.

Conditions

Advanced Breast Cancer

Keywords

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with PFS at 4 months

  The percentage of patients with advanced HRD breast cancer with PFS of 4 months or longer on talazoparib monotherapy. Disease assessment is performed by CT chest-abdomen per RECIST v 1.1.

  Baseline. During the intervention: every 2 cycles (each cycle is 28 days), preferably within 7 days before the start of every uneven cycle. Follow-up until PD, unacceptable toxicity or death. Until all patients have reached PFS endpoint (end of study).

Secondary Outcomes (2)

• Overall response rate (ORR)

  Baseline. During the intervention: every 2 cycles (each cycle is 28 days), preferably within 7 days before the start of every uneven cycle. Follow-up until PD, unacceptable toxicity or death. Until all patients have reached PFS endpoint (end of study).

• Overall survival (OS)

  Time from first administration of talazoparib to time of death due to any cause. Follow-up on survival at least every 3 months for year 1, every 6 months for year 2 and 3 and annually until death. Until all patients have reached PFS (end of study).

Other Outcomes (4)

• Molecular aberrations in HR genes

  A second biopsy at pre-screening

• PFS rate in relation to BRCA1/2 aberrations

  A second biopsy at pre-screening

• Reversion of HRD phenotype

  A second biopsy at pre-screening and optional: a biopsy at PD (immediately after the intervention). Until all patients have reached PFS endpoint (end of study).

Study Arms (1)

Talazoparib

EXPERIMENTAL

Talazoparib Capsule, oral use 1 mg per day until PD or unacceptable toxicity

Drug: Talazoparib

Interventions

Talazoparib DRUG

Talazoparib is administered daily as single agent, 1 mg orally until unacceptable toxicity or progression of disease.

Also known as: Talazoparib 1 MG Oral Capsule [Talzenna]

Talazoparib

Eligibility Criteria

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

You may qualify if:

• WHO performance status 0-2
• Locally advanced breast cancer without options for treatment with curative intent or metastatic breast cancer
• Objective progressive disease (PD) according to RECIST within 4 months prior to study entry
• The breast cancer must be either
• high grade (Bloom \& Richardson grade 3) ER positive (\>10%) and HER2 negative primary breast cancer, or
• triple negative (ER\<10%, PR\<10% and HER2 negative), or
• any Bloom \& Richardson grading and receptor status and also
• at least one metastatic lesion must have a proven HRD phenotype based on a RECAP test not treated with anticancer therapy thereafter or
• the patient must have a proven germline or somatic BRCA1 and/or BRCA2 mutation The Bloom \& Richardson grading is always based on the primary tumor. The receptor status can be based on the primary tumor or a metastatic lesion whichever comes latest.
• The site of the metastatic lesion (or primary tumor in case it is still in situ) should be easily amendable for biopsy. NB lung metastases (high risk of hemato/pneumo-thorax) and bone metastases (not suitable for RECAP test because calcifications interfere with experimental procedures) are excluded. The local guidelines will be used for stopping and r estarting of anticoagulation. Bilirubin \<1.5 ULN (except elevated bilirubin due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin) and both AST and ALT \<5x ULN in case a liver biopsy is planned.
• The tumor must be HRD, defined as HRD identified by the RECAP test determined just before the start of potential Talazoparib treatment within this study (also in case a proven germline BRCA1/2 mutation is present).
• Maximum of four prior lines of chemotherapy for advanced disease; Patients who received platinum compounds are eligible if they have had at least a progression free interval of four months.
• Measurable or evaluable disease according to RECIST 1.1 criteria (appendix 2)
• Life expectancy ≥ 3 months
• Hemoglobin ≥ 10 g/dL (6,2 mmol/L) and ANC of ≥ 1.5 x 109 /L

You may not qualify if:

• Any psychological condition potentially hampering compliance with the study protocol
• Any treatment with investigational antitumor drugs within 28 days prior to receiving the first dose of investigational treatment; or within 21 days for standard chemotherapy; or within 14 days for weekly scheduled chemotherapeutic regimens or endocrine therapy
• Radiotherapy within the last four weeks prior to receiving the first dose of investigational treatment; except 1 or 2 x 8 Gy for pain palliation, then seven days interval after the last radiation should be maintained
• Known persistent (\>4 weeks) ≥ Grade 2 toxicity from prior cancer therapy (except for alopecia grade 2)
• Symptomatic brain or leptomeningeal metastases. Patients completely free of symptoms and without corticosteroids for at least four weeks after adequate treatment by resection and/or irradiation could be eligible (consult PI).
• Women who have a positive pregnancy test (urine/serum) and/or who are breastfeeding
• Unreliable contraceptive methods. Women and men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: intra-uterine devices or systems, condom or other barrier contraceptive measures, sterilization and true abstinence)
• Concomitant use of P-gp inhibitors or inducers or BCRP inhibitors (see Appendix A)
• Any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
• Uncontrolled infectious disease (such as Human Immunodeficiency Virus HIV-1 or HIV-2 infection) or known active hepatitis B or C
• Recent myocardial infarction (\< six months) or unstable angina

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Leiden University Medical Center: collaborator
• University Medical Center Groningen: collaborator

Study Sites (3)

Leiden University Medical Center

Leiden, South Holland, 2333ZA, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, South Holland, 3015GD, Netherlands

RECRUITING

Groningen University Medical Center

Groningen, 9713GZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

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

Study Officials

• Agnes Jager, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Center

CONTACT

0031107041566; secretariaatctc@erasmusmc.nl

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: Principal Investigator

Study Record Dates

• First Submitted: November 16, 2023
• First Posted: January 5, 2024
• Study Start: September 16, 2019
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: February 28, 2025

Record last verified: 2025-02

Locations

NL (3)