Clinical Study of Camrelizumab Combined With TCb Versus TCb in Neoadjuvant Treatment of Triple-negative Breast Cancer

A Randomized, Open Label, Parallel Controlled, Multicenter Phase II Clinical Study of Carelizumab Combined With TCb (Docetaxel+Carboplatin) Versus TCb Neoadjuvant Therapy for Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a special subtype of breast cancer that lacks the expression of ER, PR, and Her-2 proteins, accounting for 15%-20% of all breast cancers.TNBC patients do not benefit from endocrine therapy or HER-2-targeted therapy, but are sensitive to cytotoxic drug therapy.Although the survival of TNBC patients has improved significantly compared with the past, it is still the type with the worst prognosis among all subtypes of breast cancer. Methods and drugs to further improve the therapeutic effect of TNBC patients are still being explored.

Camrelizumab, a PD-1 inhibitor produced by Hengrui, has been approved for the treatment of various malignant tumors including advanced lung cancer, advanced liver cancer and advanced esophageal cancer. Shows good therapeutic effect and safety.

Therefore, this study intends to explore the superiority of camrelizumab on the basis of the less toxic anthracycline-free TCb regimen.In order to provide more effective and safe neoadjuvant therapy for lymph node-positive TNBC patients.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Triple Negative Breast Cancer; Camrelizumab
• Intervention / Treatment: Drug: （Carrelizumab + TCb） regimen; Drug: TCb regimen

Detailed Description

This study mainly compared the efficacy and safety of 6*TCb (docetaxel+carboplatin)+carrelizumab regimen and 6*TCb regimen in neoadjuvant chemotherapy for triple-negative breast cancer.

Patients who met the inclusion criteria were randomly assigned to the experimental group and the control group in a 2:1 ratio.

• The experimental group received 6 cycles of TCb+carrelizumab (docetaxel 75mg/m2 on the first day + carboplatin AUC=6, on the first day; camrelizumab 200mg on the third day) regimen neoadjuvant chemotherapy, every 21 days is a cycle.
• The control group received 6 cycles of TCb (docetaxel 75mg/m2 on the first day + carboplatin AUC=6 on the first day) regimen neoadjuvant chemotherapy, every 21 days as a cycle.

The efficacy and safety of the two chemotherapy regimens on neoadjuvant chemotherapy for triple-negative breast cancer were evaluated by PCR, EFS, DFS, DDFS and ORR after surgery.

• Study Type: Interventional
• Enrollment (Estimated): 369
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhenzhen Liu; Phone Number: 13603862755; Email: liuzhenzhen73@126.com
• Study Contact Backup: Name: Dechuang Jiao; Phone Number: 13598004327; Email: jiaodechuang@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Zhen Liu; Phone Number: 18603723729

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age: 18-70 years old
2. cT2 - cT4d, or cT1c with axillary lymph node metastasis confirmed clinically and pathologically；

3. Pathologically proven triple negative breast cancer:

   Triple-negative breast cancer is defined as:

   • Negative for ER and PR (IHC nuclear staining <10%)
   • Her-2 negative (IHC 0, 1+ without FISH, or IHC 2+ with no amplification by FISH)；
4. Has clinically measurable lesions:Measurable lesions on ultrasound, mammography, or MR (optional) within 1 month before randomization；
5. Organ and bone marrow function tests within 1 month before chemotherapy suggest no contraindications to chemotherapy；
6. Cardiac ultrasound EF value ≧55%；
7. Females of childbearing age, with a negative serum pregnancy test 14 days before randomization;
8. ECOG score≤1 point;
9. Sign informed consent；

Exclusion Criteria:

1. The patient has evidence of metastatic breast cancer；
2. For this disease, chemotherapy, endocrine therapy, targeted therapy, radiation therapy, etc. have been received;
3. The patient has a second primary malignancy other than adequately treated skin cancer;
4. The patient has been treated with anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death ligand 1 (anti-PD-L1) or anti-PD-L2 drugs, or other immunotherapy；
5. The patient has been diagnosed with immunodeficiency disease or autoimmune disease;
6. The patient has severe lung or heart disease;
7. The patient has active hepatitis B and C;
8. The patient has a history of organ transplantation or bone marrow transplantation;
9. pregnant or breastfeeding women;
10. The investigators considered chemotherapy contraindicated due to serious, uncontrolled other medical conditions.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: （Carrelizumab + TCb） regimen; The experimental group received 6 cycles of TCb+carrelizumab (docetaxel 75mg/m2 on the first day + carboplatin AUC=6, on the first day; camrelizumab 200mg on the third day) regimen neoadjuvant chemotherapy, every 21 days is a cycle.	Drug: （Carrelizumab + TCb） regimen; Carrelizumab +docetaxel + carboplatin regimen; Other Names: Carrelizumab +docetaxel + carboplatin
Placebo Comparator: TCb regimen; The control group received 6 cycles of TCb (docetaxel 75mg/m2 on the first day + carboplatin AUC=6 on the first day) regimen neoadjuvant chemotherapy, every 21 days as a cycle.	Drug: TCb regimen; docetaxel + carboplatin regimen; Other Names: docetaxel + carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response rate (pCR rate)	After neoadjuvant chemotherapy and surgery, the resected specimen (breast + axilla) was free of any invasive cancer (ie, ypT0/is, ypN0)	up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-Free Survival (EFS)	EFS was defined as the time from randomization to any of the following events: disease progression during neoadjuvant therapy, local or distant recurrence, second primary malignancy (breast or other cancer), or death from any cause.	5-10 years after surgery.
DFS	Disease-free Survival,From the date of surgery to the first local, regional, contralateral or distant recurrence, and death from any cause	5-10 years after surgery
Distant Disease Free Survival (DDFS)	DDFS is defined as the time from surgery to distant recurrence or death from any cause	5-10 years after surgery
Objective Response Rate (ORR)	ORR is defined as the number of target lesion responders as assessed by MRI	Preoperative
number of adverse events	Evaluate the nature, incidence and severity of chemotherapy adverse events according to CTCAE 5.0	After each cycle of chemotherapy (21 days as 1 cycle)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression of PD-L1	Differences in the benefits of carelizumab under different PD-L1 expression status	up to 24 weeks
gene mutation rate	Predictive value of polygenic analysis in the population benefiting from camrelizumab	up to 24 weeks

Collaborators and Investigators

• Sponsor: Zhenzhen Liu
• Investigators: Principal Investigator: Zhenzhen Liu, Study Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: July 24, 2022
• First Posted (Actual): July 27, 2022

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Triple Negative Breast Cancer; Neoadjuvant chemotherapy; Disease-free survival; Camrelizumab; Pathological complete response rate
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Carboplatin
• Other Study ID Numbers: HELEN-011

Drug and device information, study documents

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