PARPi or Capecitabine Combined With PD-1 Inhibitors as Adjuvant Therapy in High-risk TNBC

NCT06533384 | Recruiting Phase 3 DMC

• 1 other identifier: KY2023-800
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 1

Brief Summary

In TNBC patients who have completed neoadjuvant immunotherapy and local treatment, a 9-cycle regimen of PD-1 inhibitor adjuvant immunotherapy is currently considered the standard approach. Based on the classification according to their BRCA mutation status, patients with BRCA mutations choose the PD-1 inhibitor + PARPi regimen, while patients without BRCA mutations opt for the PD-1 inhibitor + capecitabine regimen. Compared to monotherapy with PD-1 inhibitors, these combination regimens may offer improved efficacy and acceptable tolerability. This study is designed as a prospective, randomized, controlled, open-label, single-center phase III trial aimed at assessing the efficacy and safety of selecting PARPi or capecitabine in combination with PD-1 inhibitors based on germline BRCA1/2 mutations as adjuvant therapy in high-risk TNBC patients who have achieved non-pCR after completion of neoadjuvant immunotherapy in conjunction with chemotherapy and local treatment.

Conditions

Triple-negative Breast Cancer

Outcome Measures

Primary Outcomes (1)

• IDFS

  invasive disease free survival

  Up to approximately 5 years

Secondary Outcomes (3)

• OS

  Up to approximately 5 years

• DDFS

  Up to approximately 5 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Up to approximately 5 years

Study Arms (2)

Experimental ARM

EXPERIMENTAL

In the experimental group, patients with confirmed deleterious mutations based on germline BRCA1/2 status receive a combination of Fuzuloparib and Camrelizumab as adjuvant therapy. Patients without germline BRCA1/2 deleterious mutations receive a combination of capecitabine and Camrelizumab as adjuvant therapy.

Drug: As per the germline BRCA1/2 mutation status, the selection of either Fuzuloparib or capecitabine in combination with Camrelizumab is made for adjuvant therapy.

Control ARM

ACTIVE COMPARATOR

9 cycles of Camrelizumab as adjuvant therapy.

Drug: As per the germline BRCA1/2 mutation status, the selection of either Fuzuloparib or capecitabine in combination with Camrelizumab is made for adjuvant therapy.; Drug: 9 cycles of Camrelizumab as adjuvant therapy.

Interventions

As per the germline BRCA1/2 mutation status, the selection of either Fuzuloparib or capecitabine in combination with Camrelizumab is made for adjuvant therapy. DRUG

As per the germline BRCA1/2 mutation status, the selection of either Fuzuloparib or capecitabine in combination with Camrelizumab is made for adjuvant therapy.

Control ARM; Experimental ARM

9 cycles of Camrelizumab as adjuvant therapy. DRUG

9 cycles of Camrelizumab as adjuvant therapy.

Control ARM

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed invasive breast cancer.
• Negative expression of estrogen receptor (ER) and progesterone receptor (PR) according to immunohistochemistry (i.e., tumor cells showing positive staining in less than 1% of all tumor cells).
• Negative human epidermal growth factor receptor 2 (HER2) status as determined by immunohistochemistry: HER2 score of 0/1+ or, if the score is 2+, HER2/CEP17 ratio less than 2.0 or HER2 gene copy number less than 4, as confirmed by in situ hybridization (ISH).
• Clinical tumor staging: T1c, N1-N2 or T2, N0-N2 or T3, N0-N2 or T4a-d, N0-N2.
• The subjects were required to have good organ function, as evidenced by the following tests conducted within 7 days before randomization:
• Hematology examination (excluding blood transfusion or use of hematopoietic stimulating agents for correction):
• Hemoglobin (Hb) ≥ 90 g/L.
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
• Absolute lymphocyte count (ALC) ≥ 0.5 × 109/L.
• Platelet count (PLT) ≥ 100 × 109/L.
• White blood cell count (WBC) ≥ 3.0 × 109/L and ≤ 15 × 109/L.
• Serum biochemistry examination (excluding recent blood transfusion or albumin administration):
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of normal (ULN).
• Alkaline phosphatase (ALP) ≤ 2.5 ULN.
• Total bilirubin (TBIL) ≤ 1.5 ULN.

You may not qualify if:

• Known history of allergy to the components of the investigational drug.
• Previous receipt of antitumor treatment or radiation therapy for any malignancy (excluding previously cured cervical carcinoma in situ and basal cell carcinoma).
• Undergone major surgery unrelated to breast cancer within the past 4 weeks, or patients who have not fully recovered from such surgery.
• Inability to swallow, intestinal obstruction, or other factors that may affect the administration and absorption of the medication.
• Severe cardiac disease or discomfort that prevents treatment.
• Presence of mental illness or substance abuse that interferes with compliance.
• Pregnant or breastfeeding women.
• Concurrent participation in other clinical trials.

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

Study Sites (1)

Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University

Guangzhou, Guangdong, 510080, China

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Kun Wang, MD

  Guangdong Provincial People's Hospital

  STUDY CHAIR

Central Study Contacts

Liulu Zhang, MD

CONTACT

+86 020-83827812-80410; zhangliulu@gdph.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2024
• First Posted: August 1, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2030
• Last Updated: November 4, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)