A Phase Ⅱ Study to Evaluate the Efficacy and Safety of Camrelizumab Plus Chemotherapy as Neoadjuvant Therapy With Triple Negative Breast Cancer (TNBC)
Overview
- Phase
- Phase 2
- Intervention
- Camrelizumab
- Conditions
- Triple Negative Breast Cancer (TNBC)
- Sponsor
- Aiping Shi
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Pathological Complete Response (pCR)
- Status
- Recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of Camrelizumab plus chemotherapy as neoadjuvant therapy and Camrelizumab as adjuvant therapy in participants who have triple negative breast cancer (TNBC).
Detailed Description
After a screening phase of approximately 28 days, each participant will receive neoadjuvant study treatment (camrelizumab + chemotherapy) for approximately 24 weeks (8 cycles). Each participant will then undergo definitive surgery 2-4 weeks after the last cycle of the neoadjuvant treatment. After definitive surgery, each participant will receive adjuvant study treatment (camrelizumab) for approximately 27 weeks (9 cycles). Following adjuvant study treatment, each participant will be monitored for safety, survival and disease recurrence. The primary study hypothesis is that camrelizumab is superior to chemotherapy, in combination with chemotherapy, as measured by the rate of Pathological Complete Response (pCR), Event-free Survival (EFS) and Objective Overall Response Rate (ORR) in participants with TNBC.
Investigators
Aiping Shi
The First Hospital of Jilin University
Jilin University
Eligibility Criteria
Inclusion Criteria
- •18-70 Years, female;
- •Histologically documented Triple Negative Breast Cancer (TNBC) patients;
- •The subtypes of TNBC patients should include basal cell-like subtypes (BL1, BL2), Luminal androgenic type (LAR), and other types, such as mesenchymal type (M), mesenchymal stem cell type (MSL) and immunomodulatory type (IM);
- •Previously untreated non-metastatic (M0) TNBC, the primary tumor (T) and regional lymph node (N) combined staging determined by the investigator based on radiological and/or clinical evaluation. Stage at presentation: T1c, N1-N2; T2, N0-N2; T3, N0-N2;
- •Promising radical surgical treatment;
- •At least one measurable lesion according to RECIST 1.1;
- •Life expectancy is not less than 3 months;
- •Adequate function of major organs meets the following requirements:
- •Neutrophils ≥ 1.5×10\^9/L Hemoglobin ≥ 90g/L Platelets ≥ 100×10\^9/L Total bilirubin≤ 1.5 × the upper limit of normal (ULN) ALT and AST ≤ 2.5 × ULN Serum creatinine ≤1.5 × ULN, Endogenous creatinine clearance ≥50mL/min;
- •Left ventricular ejection fraction (LVEF) ≥50% or ≥ limit of normal (LLN) was evaluated by echocardiography (ECHO) or Multigated Acquisition (MUGA);
Exclusion Criteria
- •Has participated in an interventional clinical study with an investigational compound within 4 weeks prior to initiation of study treatment;
- •Prior treatment with anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibodies;
- •Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer;
- •Active or history of autoimmune disease or immune deficiency diseases except history of autoimmune-related hypothyroidism, controlled Type 1 diabetes mellitus;;
- •Has a history of (non-infectious) pneumonitis, interstitial lung disease or uncontrollable systematicness diseases, including pulmonary fibrosis, acute lung disease, etc.;
- •Administration of a live attenuated vaccine within 30 days prior to initiation of study treatment or anticipation of need for such a vaccine during the study;
- •Has active infection (CTCAE≥2) needed the treatment of antibiotic within 2 weeks prior to initiation of study treatment;
- •Has a history of serious cardiovascular disease, including myocardial infarction, acute coronary syndrome or coronary angioplasty/stent implantation/bypass grafting history in the past 6 months, and have level II-IV congestion Heart failure (CHF), or III NYHA and IV CHF history;
- •Prior allogeneic stem cell or solid organ transplantation
- •History of neurological or psychiatric disorders, including schizophrenia, severe depressive disorder, bipolar disorder, etc.;
Arms & Interventions
Camrelizumab+Chemotherapy
PD-1+AC-T: Participants receive Camrelizumab Q3W + doxorubicin Q3W + cyclophosphamide Q3W for 4 cycles, followed by Camrelizumab Q3W + docetaxel Q3W for 4 cycles as neoadjuvant therapy prior to surgery,followed by 9 cycles of Camrelizumab Q3W as adjuvant therapy post-surgery. PD-1+TA: Participants receive Camrelizumab Q3W for 8 cycles , docetaxel Q3W + doxorubicin Q3W for 4 cycles as neoadjuvant therapy prior to surgery,followed by 9 cycles of Camrelizumab Q3W as adjuvant therapy post-surgery.
Intervention: Camrelizumab
Camrelizumab+Chemotherapy
PD-1+AC-T: Participants receive Camrelizumab Q3W + doxorubicin Q3W + cyclophosphamide Q3W for 4 cycles, followed by Camrelizumab Q3W + docetaxel Q3W for 4 cycles as neoadjuvant therapy prior to surgery,followed by 9 cycles of Camrelizumab Q3W as adjuvant therapy post-surgery. PD-1+TA: Participants receive Camrelizumab Q3W for 8 cycles , docetaxel Q3W + doxorubicin Q3W for 4 cycles as neoadjuvant therapy prior to surgery,followed by 9 cycles of Camrelizumab Q3W as adjuvant therapy post-surgery.
Intervention: Doxorubicin
Camrelizumab+Chemotherapy
PD-1+AC-T: Participants receive Camrelizumab Q3W + doxorubicin Q3W + cyclophosphamide Q3W for 4 cycles, followed by Camrelizumab Q3W + docetaxel Q3W for 4 cycles as neoadjuvant therapy prior to surgery,followed by 9 cycles of Camrelizumab Q3W as adjuvant therapy post-surgery. PD-1+TA: Participants receive Camrelizumab Q3W for 8 cycles , docetaxel Q3W + doxorubicin Q3W for 4 cycles as neoadjuvant therapy prior to surgery,followed by 9 cycles of Camrelizumab Q3W as adjuvant therapy post-surgery.
Intervention: Cyclophosphamide
Camrelizumab+Chemotherapy
PD-1+AC-T: Participants receive Camrelizumab Q3W + doxorubicin Q3W + cyclophosphamide Q3W for 4 cycles, followed by Camrelizumab Q3W + docetaxel Q3W for 4 cycles as neoadjuvant therapy prior to surgery,followed by 9 cycles of Camrelizumab Q3W as adjuvant therapy post-surgery. PD-1+TA: Participants receive Camrelizumab Q3W for 8 cycles , docetaxel Q3W + doxorubicin Q3W for 4 cycles as neoadjuvant therapy prior to surgery,followed by 9 cycles of Camrelizumab Q3W as adjuvant therapy post-surgery.
Intervention: Docetaxel
Outcomes
Primary Outcomes
Pathological Complete Response (pCR)
Time Frame: Up to approximately 12-30 weeks
pCR rate is defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants
Secondary Outcomes
- Event-Free Survival (EFS)(Up to approximately 2 years)
- Objective Overall Response Rate (ORR)([Time Frame: Up to approximately 12-30 weeks])
- Overall survival (OS)(Up to approximately 2 years)
- Adverse events (AEs)(Up to approximately 35 weeks)