Talazoparib in Advanced Breast Cancer Patients With Homologous Recombinant Deficiency

NCT04892693 | Recruiting Phase 2

• 1 other identifier: H-2009-079-1157
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Talazoparib has shown clinical efficacy in breast cancer patients with germline BRCA1 or BRCA2 mutations. Beyond BRCA1 and BRCA2 mutations, it is plausible that talazoparib may have activity in patients with homologous recombination defects (HRD).

Conditions

Advanced Breast Cancer

Keywords

homologous recombinant deficiency; biomarker study of talazoparib; talazoparib; germline; BRCA

Outcome Measures

Primary Outcomes (1)

• Response rate (RR)

  Defined as a complete response (CR) or partial response (PR) on two consecutive assessments, at least 28 days apart, as determined by investigator assessment using RECIST v1.1

  Enrollment to end of treatment up to 2 years

Secondary Outcomes (5)

• Progression-free survival (PFS)

  First day of study treatment to the date of disease progression or death due to any cause, whichever came first, assessed up to 2 years

• Duration of objective response (DOR)

  Enrollment to end of treatment up to 2 years

• Clinical benefit rate (CBR)

  Enrollment to end of treatment up to 2 years

• Overall survival (OS)

  First day of study treatment to the date of death due to any cause, assessed up to 2 years

• Safety profile (Treatment-related adverse events as assessed by CTCAE v4.0)

  First day of study treatment to end of treatment, assessed up to 2 years

Study Arms (1)

Talazoparib

EXPERIMENTAL

; Talazoparib should be taken orally once daily (ie, continuous daily dosing) at approximately the same time each day (preferably in the morning). 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 discretion of the treating physician.

Drug: Talazoparib Oral Capsule

Interventions

Talazoparib Oral Capsule DRUG

\- Patients will receive Talazoparib 1 mg orally once daily continuously, with or without food. Laboratory values will be monitored every 4 weeks until progression or unacceptable toxicity. Dose modifications should be made based on the observed toxicity

Also known as: Single arm; Talazoparib

Talazoparib

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥19 years old.
• Pathologically documented breast cancer that is unresectable or metastatic
• Tumor with homologous recombination deficiency (HRD) defined by
• Germline or Somatic BRCA1/2 mutation
• Homologous recombination repair (HRR) genes mutation
• HRD detected through RAD51 foci formation functional assay
• HRR genes: ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L
• Previously treated with a taxane, unless this treatment was contraindicated (whether in recurrent/metastatic setting or in neoadjuvant/adjuvant setting).
• Previous treatment with platinum therapy in the advanced or metastatic setting is permitted, provided the patient did not have a progression during the platinum treatment. If the patient was treated with neoadjuvant or adjuvant platinum therapy, at least 6 months of disease-free interval is required after the last dose.
• Documented radiologic progression (during or after most recent treatment or within 6 months after completing adjuvant therapy).
• \- If the patients had relapsed within 6 months after adjuvant therapy, this will be counted as a systemic chemotherapy for advanced or metastatic disease.
• At least 3 weeks has passed since last chemotherapy treatment
• At least 2 weeks has passed since last hormone therapy or radiation therapy (including palliative radiation).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1
• At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging \[MRI\] where CT is not feasible) and is suitable for repeated assessment as per RECIST v.1.1.

You may not qualify if:

• Prior treatment PARP inhibitor
• However, if the patient participated in a clinical trial evaluating adjuvant PARP inhibitor, patient is allowed to be included in the present study if the patient recurred 6 months after completing PARP inhibitor. No more than three line of previous systemic chemotherapy, excluding neo-adjuvant and adjuvant chemotherapy. (No limitation on hormone therapy. Hormone therapy is not counted as previous line)
• If there is a standard treatment available for metastatic breast cancer.
• History of another primary malignancy except for
• Malignancy treated with curative intent and with no known active disease ≥3 years
• contralateral breast cancer
• Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease
• Patients with GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled GI disease (e.g., Crohn's disease, ulcerative colitis)
• History of leptomeningeal carcinomatosis
• Brain metastases or spinal cord compression.
• \- Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• active infection or immunocompromised patients including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B , hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies).
• \- Subjects with simple HBV carrier, a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Patients who have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the study agents or their excipients.

Sponsors & Collaborators

• Seoul National University Hospital: lead

Study Sites (1)

Seoul National University Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Interventions

talazoparib

Study Officials

• Seock-Ah Im, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Seock-Ah Im, MD, PhD

CONTACT

82-2-2072-0850; moisa@snu.ac.kr

Yuri Park, RN

CONTACT

82-2-3668-7088; sesame1025@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

Model Details: Single arm, phase II study

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 19, 2021
• Study Start: May 25, 2021
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: April 17, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)