Neoadjuvant Camrelizumab and Fluzoparib and Nab-paclitaxel in Early Breast Cancer With HRR Gene Mutation (IMPARP)

A Phase II Study of Camrelizumab, Fluzoparib and Nab-paclitaxel in Neoadjuvant Therapy of Her-2 Negative Breast Cancer Patients With HRR Gene Mutation

This study is to evaluate the efficacy and safety of combination of Camrelizumab (Immunotherapy, PD-1 inhibitor), Fluzoparib (PARP inhibitor) and Nab-paclitaxel in neoadjuvant therapy of Her-2 negative breast cancer patients with HRR gene mutation.

Study Overview

• Status: Recruiting
• Conditions: Her-2 Negative Breast Cancer; HRR Gene Mutation
• Intervention / Treatment: Drug: Fluzoparib; Drug: Camrelizumab; Drug: Nab-paclitaxel

Detailed Description

This is a prospective, single-center, open-label phase II clinical trial investigating the activity of Camrelizumab+Fluzoparib+Nab-paclitaxel combination therapy in breast cancer patients with Her2-negative and HRR gene mutation for neoadjuvant therapy.

Anticipated 66 candidates meeting all study eligibility criteria will receive 8 cycles of Nab-paclitaxel (260mg/m2) every 3 weeks, which will add Camrelizumab (200mg, d1) and Fluzoparib (100mg BID) from the second cycle.

HRR gene mutation contains at least one pathogenic or likely pathogenic variant in germline or somatic BRCA1, BCRA2 and PALB2 genes, or in germline ATM, BARD1, BRIP1, CDK12, CHEK2, RAD51C, RAD51D genes.

• Study Type: Interventional
• Enrollment (Anticipated): 66
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying Lin, MD; Phone Number: 8212 +8602087755766; Email: linying3@mail.sysu.edu.cn
• Study Contact Backup: Name: Xiaying Kuang, MD; Phone Number: 8212 +8602087755766; Email: kuangxy5@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • First Affiliated Hospital, Sun Yat-Sen University
      • Contact: Ying Lin, MD; Phone Number: 8212 +8602087755766; Email: linying3@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically documented Her-2 negative
• TNM stage: T1c, N1-N2；T2-4, N0-N2；any T, N3
• No distant metastatic disease
• Eastern Cooperative Oncology Group Performance Status: 0~1
• HRR gene mutation: at least one pathogenic or likely pathogenic variant in germline or somatic BRCA1, BCRA2 and PALB2 genes, or in germline ATM, BARD1, BRIP1, CDK12, CHEK2, RAD51C, RAD51D genes.

Exclusion Criteria:

• Patients who are pregnant or lactating at the time of randomization or refuse to contraception.
• Patients who have other malignant diseases within 2 years, except for cured skin basal cell carcinoma, breast carcinoma in situ or cervical carcinoma in situ
• Patients with psychiatric disorder, peripheral or central nerve system disease or any disorder, which compromises ability to give informed consent or participate in this study.
• Patients who have myocardial infarction or congestive heart failure, or other serious cardiac disease.
• Patients who have used immunosuppressive drug or corticosteroids within 14 days.
• Patients who have other diseases which researchers.
• Patients who allergy to any of the drugs in this trail.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Camrelizumab, Fluzoparib and Nab-paclitaxel; Participants who confirmed pathogenic or likely pathogenic HRR gene mutation received Camrelizumab and Fluzoparib with nab-paclitaxel from the second cycle followed by nab-paclitaxel for one cycle.	Drug: Fluzoparib; Fluzoparib; Drug: Camrelizumab; Camrelizumab at a fixed dose of 200mg via IV infusion on Days 1 each 21-day cycle. Fluzoparibat at a fixed dose of 100mg BID, each 21-day cycle. Nab-paclitaxel at a fixed dose of 260 milligrams via intravenous (IV) infusion on Days 1 each 21-day cycle.; Drug: Nab-paclitaxel; Nab-paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathologic Complete Response (pCR)	Pathologic response will be assessed in the surgically resected cancer and lymph nodes after completion of all chemotherapy by the local pathologist as part of routine care. Pathologic complete response is defined as no invasive cancer in the resected breast tissue and lymph nodes (ypT0/Tis, ypN0).	Up to 32 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as percentage of participants with Complete Response and Partial Response	Up to 32 weeks
Residual Cancer Burden (RCB)	Pathologilly assessed residual cancer burden according to MD Anderson protocol.	Up to 32 weeks
Event-Free Survival (EFS)	EFS was defined as the time from the date of randomization to the date of events from any cause.	Up to 20 years
Overall Survival (OS)	OS was defined as the time from the date of randomization to the date of death from any cause.	Up to 20 years
Safety of drugs	Adverse effects of the candidates according to NCI-CTCAE 5.0	Up to 32 weeks

Collaborators and Investigators

• Sponsor: Ying Lin
• Investigators: Study Chair: Ying Lin, MD, Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2022
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): December 31, 2028

Study Registration Dates

• First Submitted: December 24, 2022
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Estimate): March 9, 2023

Study Record Updates

• Last Update Posted (Estimate): March 9, 2023
• Last Update Submitted That Met QC Criteria: March 7, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: 20220430GD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No