Phase II Study of Niraparib in Metastatic TNBC Patients With Homologous Recombination Deficiency

NCT05461690 | Unknown Phase 2

• 1 other identifier: IRB-2022-329
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

The incidence of homologous recombination deficiency in metastatic triple negative breast cancer was 52%-59%，PARP plays a key role in sensing DNA damage and converting it into intracellular signals that activate the base excision repair (BER) and single-strand break repair pathways. Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a subset of cancer cells with deficiencies in DNA repair pathways. This is a multicenter, single-arm, phase II study evaluating the efficacy and safety of niraparib in patients with HRD positive metastatic triple negative breast cancer.

Conditions

Homologous Recombination Deficiency; Triple Negative Breast Cancer

Keywords

homologous recombination deficiency; Niraparib; triple negative breast cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of patients who achieved a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by the Investigator: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.

• Clinical Benefit Rate (CBR)

  From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.

• Time to response (TTR)

  From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.

• Overall survival (OS)

  From date of first dose until the date of death from any cause, assessed up to 60 months.

Study Arms (1)

Niraparib group

EXPERIMENTAL

200mg once a day for patients with body weight \<77kg or baseline platelet count \<150,000/µL, and 300mg once a day for patients with body weight ≥ 77kg and baseline platelet count ≥ 150,000/µL until disease progression or intolerable toxicity whichever occurs first.

Drug: Niraparib

Interventions

Niraparib DRUG

200mg once a day for patients with body weight \<77kg or baseline platelet count \<150,000/µL, and 300mg once a day for patients with body weight ≥ 77kg and baseline platelet count ≥ 150,000/µL until disease progression or intolerable toxicity whichever occurs first.

Also known as: Zejula

Niraparib group

Eligibility Criteria

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

You may qualify if:

• Patient is female at least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Life expectancy longer than 6 months.
• Patients with histologically confirmed metastatic breast cancer must have disease that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative (ie, TNBC).
• Patient has measurable lesions by RECIST v1.1.
• Patients has archival tumor tissue available or a fresh biopsy must be obtained prior to study treatment initiation for HRD test. The HRD test results must be positive (HRR mutation or/and HRD score≥42).
• Patients had received no more than two previous chemotherapy regimens for metastatic disease, and they had received neoadjuvant or adjuvant treatment or treatment for metastatic disease with an anthracycline (unless it was contraindicated) or a taxane.
• Previous neoadjuvant or adjuvant treatment with platinum or/and anthracycline were allowed if at least 6 months had elapsed since the last dose. Previous treatment with platinum or/and anthracycline for metastatic disease were allowed if there was no evidence that disease progression had occurred during treatment.
• Patient has adequate organ function, defined as:
• Absolute neutrophil count (ANC) ≥ 1,500/μL(growth factor support treatment shall not be used within 7 days after the start of study treatment）
• Platelets ≥ 100,000/μL(platelet transfusion or any form of platelet raising therapy shall not be used within 2 weeks after the start of the study)
• Hemoglobin ≥ 9 g/dL(blood transfusion shall not be used within 2 weeks after the start of study treatment. EPO support treatment shall not be used within 7 days after the start of study treatment.)
• Serum creatinine ≤ 1.5× upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels \> 1.5× institutional ULN
• Total bilirubin ≤ 1.5× ULN OR direct bilirubin ≤ 1× ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in which case they must be ≤ 5× ULN

You may not qualify if:

• Patients have received PARP inhibitors for metastatic breast cancer.
• Patients who are concurrently participating in any interventional clinical trial and have received an investigational therapy ≤ 4 weeks prior to initiation of protocol therapy or within at least 5 elimination half-lives of the investigational drug.
• Patients who have received radiotherapy with \> 20% bone marrow coverage before treatment initiation, except for minor palliative radiotherapy within 1 weeks prior to enrollment.
• Patients with visceral crisis requiring chemotherapy.
• Patients with hypersensitivity to nilaparib.
• Patients receiving blood transfusions (platelets or red blood cells) ≤ 4 weeks prior to starting protocol therapy.
• Patients who have received colony-stimulating factors (eg, granulocyte-colony stimulating factor \[g-CSF\], granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) 4 weeks prior to starting protocol therapy.
• Known history of platelet transfusions for chemotherapy-induced thrombocytopenia or ≥ Grade 3 hematologic toxicity from prior cancer therapy (lasting \> 4 weeks and associated with most recent therapy).
• Patient has any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
• Patient has a serious, uncontrolled medical condition, non-malignant systemic disease, or active, uncontrolled infection.
• Patient has other types of cancer ≤ 2 years prior to starting protocol therapy.
• Patients with symptomatic brain metastasis or leptomeningeal metastasis.
• Patients with prior allogeneic bone marrow transplant or cord blood transplant.
• Patients who cannot swallow oral medication.
• Patients with gastrointestinal disorders that could interfere with absorption of the study drug.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead
• Sun Yat-sen University: collaborator
• Hunan Cancer Hospital: collaborator
• Fujian Cancer Hospital: collaborator
• Zhejiang University: collaborator
• Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University: collaborator

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

niraparib

Condition Hierarchy (Ancestors)

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

Study Officials

• Xiaojia Wang, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaojia Wang, MD

CONTACT

13906500190; wxiaojia0803@163.com

Wenming Cao, MD, PhD

CONTACT

13858064001; caowm@zjcc.org.cn

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: Director

Study Record Dates

• First Submitted: June 27, 2022
• First Posted: July 18, 2022
• Study Start: September 1, 2022
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: July 18, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share