Chidamide Combined With Zimberelimab in the Treatment of Metastatic Triple-negative Breast Cancer Patients

The Efficacy and Safety of Chidamide Combined With Zimberelimab in the Treatment of Metastatic Triple-negative Breast Cancer Patients: A Single-armed, Phase II Trial

The objective of this study is to evaluate the efficacy and safety of a new treatment regimen (Chidamide combined with Zimberelimab) in the treatment of patients with metastatic triple negative breast cancer after the second-line therapy.

Study Overview

• Status: Recruiting
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Drug: Chidamide combined with Zimberelimab

Detailed Description

This is a phase II, single center, prospective, single arm clinical trial. The objective of the study is to evaluate the efficacy and safety of a new treatment regimen (Chidamide combined with Zimberelimab) in the treatment of patients with metastatic triple negative breast cancer after the second-line therapy. This study plans to recruit 47 subjects.

• Study Type: Interventional
• Enrollment (Anticipated): 47
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhong-yu Yuan, M.D.; Phone Number: 862087342794; Email: yuanzhy@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University, Cancer Center
      • Contact: Yuan Zhong-yu, MD; Phone Number: 86-20-87342496; Email: yuanzhy@sysucc.org.cn
      • Contact: Huang Jia-Jia, MD; Phone Number: 86-20-87343794; Email: huangjiaj@sysucc.org.cn
      • Principal Investigator: Yuan Zhong-yu, MD
      • Sub-Investigator: Huang Jia-Jia, MD

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:

• Histological confirmation of triple-negative breast cancer on primary tumour at diagnosis/on biopsy of metastasis.
• At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
• Fail first-line or above anti-tumor treatment.
• Adequate organ function including bone marrow, renal function, hepatic function, and cardiac reserve.
• Compliance with the study protocol.
• Have provided written and signed informed consent.
• Minimum life expectancy 16 weeks.

Exclusion Criteria:

• Pregnant or breast feeding.
• Uncontrolled medical problems.
• Evidence of active acute or chronic infection.
• Hepatic, renal, cardiac, or bone marrow dysfunction.
• Concurrent malignancy or history of other malignancy within the last five years.
• Known severe hypersensitivity to Chidamide or Zimberelimab
• Patients were unable or unwilling to comply with program requirements.

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: Treatment arm; Chidamide and Zimberelimab	Drug: Chidamide combined with Zimberelimab; Chidamide: 30mg each time, orally, biw; Zimberelimab, 240mg, IV, every 3 weeks.; Other Names: Chidamide (Tucidinostat)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	The proportion of patients with measurable tumor size reduction of a predefined amount (complete response [CR], partial response [PR]) according to the response evaluation criteria in solid tumors (RECIST) version 1.1. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit rate (CBR)	The proportion of patients with measurable tumor size stable lasting ≥24 weeks (stable disease [SD]) or its size reduction of a predefined amount (complete response [CR], partial response [PR]) following the response evaluation criteria in solid tumors (RECIST) version 1.1. Complete Response (CR) and Partial Response (PR) are defined in Primary Outcome Measure. Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (progressive disease), taking as reference the smallest sum diameters while on study. Progressive Disease: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (0.5 cm). (Note: the appearance of one or more new lesions is also considered progression).	18 months
Progression Free Survival (PFS)	The interval time from the date of initiation treatment for metastatic breast cancer to the date of the first documented disease progression or death due to any cause.	24 months
Overall Survival (OS)	The interval time from the date of initiation treatment for metastatic breast cancer to the date of death from any cause.	30 months
Occurrence and severity of AEs	Occurrence and severity of AEs by NCI-CTCAE v5. Changes in laboratory parameters (hematology and serum chemistry), vital signs and ECG parameters. Grade 3 or 4 abnormalities in serum chemistry laboratory parameters.	30 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers related to efficacy	Baseline tumor biopsy from metastatic or recurrent lesions was required, we analyze and compare the difference of tumor immune microenvironment among patients with different responses to this intervention via the single cell sequencing of acquired tumor biopsy. And peripheral blood samples were collected at baseline, one day before the second cycle treatment and the date of withdrawal from this clinical trial confirmed by researchers. Then peripheral blood mononuclear cell cluster analysis will be performed and compared their changes before and after treatment.	24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Zhong-yu Yuan, M.D., Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): June 15, 2022
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: November 6, 2022
• First Submitted That Met QC Criteria: November 20, 2022
• First Posted (Actual): December 1, 2022

Study Record Updates

• Last Update Posted (Actual): December 1, 2022
• Last Update Submitted That Met QC Criteria: November 20, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Chidamide plus Zimberelimab
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms
• Other Study ID Numbers: SYSUCC 019

Drug and device information, study documents

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