Fluzoparib in Combination With Chidamide or Camrelizumab for HRD Positive HER2 Negative Advanced Breast Cancer

An Open, Multi-center, Cohort Clinical Study of Fluzoparib in Combination With Chidamide or Camrelizumab for HRD Positive and HER2-negative Advanced Breast Cancer

This study is planned to include 40 patients with HER2-negative advanced breast cancer to receive fluzoparib combined with chidamide or fluzoparib combined with camrelizumab to observe and evaluate the efficacy and safety of fluzoparib combined with camrelizumab or chidamide in the treatment of HRD-positive HER2-negative advanced breast cancer.

Study Overview

• Status: Recruiting
• Conditions: Advanced HER2 Negative Breast Carcinoma; HRD+Breast Cancer
• Intervention / Treatment: Drug: fluzoparib+chidamide; Drug: fluzoparib+camrelizumab

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chunfang Hao; Phone Number: 18622223686; Email: haochf@163.com
• Study Contact Backup: Name: Silu Wang; Phone Number: 18559171530; Email: wangsiluaaron@163.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Chunfang Hao; Phone Number: 18622223686; Email: haochf@163.com
      • Contact: Silu Wang; Phone Number: 18559171530; Email: wangsiluaaron@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. histologically confirmed initial stage IV breast cancer or recurrent metastatic breast cancer; advanced treatment stage received at least 1 line of chemotherapy but no more than 2 lines of chemotherapy; hormone receptor-positive patients received at least one endocrine therapy in advanced treatment stage, or the investigator judged that they were not suitable for endocrine therapy; and patients with hormone receptor-positive advanced breast cancer who progressed within 2 years of adjuvant endocrine therapy.
2. histologically confirmed invasive HER2-negative breast cancer (specific definition: HER20-1 + or HER2 2 + by immunohistochemistry but negative or no amplification by FISH or CISH, following the 2018 version of the ASCO-CAPHER2 guidelines for negative interpretation);
3. central confirmation of HRD positivity, known germline BRCA and/or systemic BRCA mutation status is allowed to be preferred.
4. age 18-70 years
5. According to RECIST 1.1, at least one measurable lesion is present;
6. ECOG score: 0-2; expected survival more than 12 weeks;
7. Previous treatment with immune checkpoint inhibitors, PARP inhibitors and HDAC inhibitors (including chidamine, romidepsin, vorinostat, benirestat, parastat, etc.);
8. All acute toxicities caused by previous anti-tumor treatment return to the level specified in the inclusion/exclusion criteria (except alopecia and other toxicities that are considered by the investigator to pose no safety risk to the subjects);
9. Female subjects of childbearing potential need to use a medically recognized contraceptive measure during the study treatment and at least 3 months after the last use of the study drug;
10. Patients with known hormone receptor status;

11. Main organ function is basically normal, and meet the following conditions:

    1. Blood routine examination criteria need to meet: HB ≥ 90 g/L (14 without blood transfusion); ANC ≥ 1.5 × 109/L; PLT ≥ 75 × 109/L;
    2. Biochemical examination need to meet the following criteria: TBIL ≤ 1.5 × ULN (upper limit of normal); ALT and AST ≤ 3 × ULN; if there is liver metastasis, ALT and AST ≤ 5 × ULN; serum Cr ≤ 1 × ULN;
    3. cardiac function: LVEF ≥ 50%
12. The subject voluntarily joined the study and signed the informed consent form.

Exclusion Criteria:

1. Uncontrolled central nervous system metastasis (defined as symptoms or requiring glucocorticoids or mannitol to control symptoms);
2. Clinically symptomatic third space effusion, pericardial effusion, pleural effusion and abdominal effusion that cannot be controlled by pumping or other treatments;
3. Currently or recently (within 30 days before enrollment) is participating in another clinical study;
4. Five Other malignant tumors (except adequately treated cervical carcinoma in situ or skin squamous cell carcinoma or controlled skin basal cell carcinoma) within the past 4 years;
5. Uncontrolled cardiac clinical symptoms or diseases, such as: (1) NYHA grade 2 or higher heart failure (2) unstable angina pectoris (3) myocardial infarction within 1 year (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention (5) QTc > 470 ms;
6. Hyperactive/venous thrombotic events, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism;
7. He following history 24 days before signing the ICF: gastrointestinal ulcers, gastrointestinal perforation, corrosive esophagitis or gastritis, inflammatory bowel disease or inflammation, abdominal fistula, tracheoesophageal fistula or intra-abdominal abscess;
8. Factors that significantly affect oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction;
9. Patients with a clear history of allergy, Potential allergy or intolerance to cidaniline, fluzoparib, and carreizumab;
10. Human immunodeficiency virus (HIV) infection, active hepatitis B (hepatitis B surface antigen positive and HBV DNA ≥ 500 IU/ml), hepatitis C (hepatitis C antibody positive and HCV-RNA above the lower limit of detection of the analytical method);
11. Female patients during pregnancy and lactation, female patients of childbearing potential with positive baseline pregnancy test or female patients of childbearing age who are unwilling to take effective contraceptive measures throughout the trial;
12. According to the investigator's judgment, the presence of concomitant diseases (including but not limited to hypertension with poor drug control, severe diabetes, neurological or psychiatric diseases, active infection, etc.) or any other condition that seriously endangers the subject's safety, may confound the study results, or affect the subject's completion of this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fluzoparib+chidamide; Fluzoparib: 150 mg twice daily (morning and evening) for 21 consecutive days as a cycle until disease progression or intolerance. Chidamide: It is recommended to take 20 mg (4 tablets) twice a week, with an interval of no less than 3 days between doses (such as Monday and Thursday, Tuesday and Friday, Wednesday and Saturday, etc.), for 30 minutes. Until disease progression or intolerable to patient.	Drug: fluzoparib+chidamide; Arms A will be treated with fluzoparib in combination with cedaramide
Experimental: fluzoparib+camrelizumab; Fluzoparib: 150 mg twice daily (morning and evening) for 21 consecutive days as a cycle until disease progression or intolerance. Camrelizumab: 200 mg IV drip over approximately 30 minutes (no less than 20 minutes and no more than 60 minutes) on Day 1 of each 3-week treatment cycle until disease progression or intolerance.	Drug: fluzoparib+camrelizumab; Arms B will be treated with fluzoparib in combination with camrelizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR(objective response rate)	through study completion, an average of 6 months	At the end of Cycle 1 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2021
• Primary Completion (Anticipated): October 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: June 29, 2021
• First Submitted That Met QC Criteria: October 7, 2021
• First Posted (Actual): October 20, 2021

Study Record Updates

• Last Update Posted (Actual): September 29, 2022
• Last Update Submitted That Met QC Criteria: September 27, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BC-Fluzoparib

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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