SBRT, Chemotherapy, and AK104 Neoadjuvant Therapy for Triple-negative Breast Cancer (TNBC)
ConditionBreast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorHubei Cancer Hospital
About this trial
Studies have indicated that the improvement in pathological complete response (pCR) is significantly correlated with triple-negative breast cancer（TNBC）patients' overall survival (OS). Patients with TNBC have poor efficacy for neoadjuvant chemotherapy. The combination of neoadjuvant therapy with immunotherapy and chemotherapy has been demonstrated to enhance the pCR rate of TNBC patients, increasing it from 45% to approximately 60%. Therefore, how to further improve the pCR rate of TNBC breast cancer became the main objective of this study. Stereotactic radiotherapy (SBRT) not only kills tumor cells directly, but also kills the distant unirradiated tumor cells by promoting the cross-initiation of tumor-specific CD8+ T cells, a phenomenon known as the abscopal effect. Our research team has recently discovered that the triple therapy model of SBRT + anti-vascular targeting + anti-PD-1 was safe and efficacious in lung cancer patients. Cadonilimab (AK104) is an PD-1/CTLA-4 bispecific antibody. In order to improve the pCR, a single-arm, open, phase II clinical study was proposed to explore the safety and efficacy of SBRT+AK104+chemotherapy, a neoadjuvant treatment modality, in the treatment of TNBC.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Histologically confirmed ER-/PR-/HER2- invasive breast cancer patients (ER/PR immunohistochemistry negative or<1%; Her2 immunohistochemistry of 0, 1+, or 2+/FISH-) patients; patients meeting one of the following conditions: (1) tumor mass larger than 2cm, (2) the presence of axillary lymph node metastasis, and (3) the desire to conserve breasts, but the ratio of tumor size to breast volume is large and difficult to conserve breasts;
Patients aged ≥18 years old;
ECOG score of 0-1;
Biochemical test indexes before enrollment must meet the following criteria, hematologic: white blood cell count (WBC) ≥ 2.0x10^9/L; neutrophil count (ANC) ≥ 1.5×10^9/L; platelet count (PLT) ≥ 100×10^9/L; hemoglobin (Hb) ≥ 90g/L; function: total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); glutamate aminotransferase (ALT) ≤3 × ULN; aspartate aminotransferase (AST) ≤3 × ULN; renal function: creatinine (Cr) ≤1.5 × ULN; if >1.5 × ULN, creatinine clearance needs to be ≥50mL/min (calculated according to Cockcroft-Gault formula); coagulation: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN.
Disqualifiers
Received chemotherapy, targeted therapy, or radiation therapy within 12 months prior to first use of study drug;
Solid organ or blood system transplantation;
Myocardial infarction, poorly controlled arrhythmia (including QTc intervals ≥ 470 ms) within 6 months prior to first use of study drug (QTc intervals are calculated using the Fridericia formula, which is: QTc=QT/RR ^0.33);
Class III-IV cardiac insufficiency according to NYHA criteria or cardiac ultrasound: LVEF < 50%;
Trial design
Design model
Single group
Treatments tested in this trial
Cadonilimab (AK104)
Drug8Gy\*3 SBRT to irradiate the primary lesion (without axillary lymph node metastasis) or 6Gy\*3 SBRT irradiation to irradiate the primary lesion and axillary lymph node metastasis will be administered at first. And then the first cycle of chemotherapy+AK104 given within 24 hours of the end of SBRT. The total eight cycles of preoperative chemotherapy combined with immunotherapy were administered. Surgical resection was performed within 4-6 weeks after the completion of the eighth cycle of chemotherapy combined with immunotherapy. The chemotherapy regimen consisted of: Four cycles of doxorubicin 50mg/m2 (Q3W) + cyclophosphamide 600mg/m2 (Q3W) were administered, followed by four cycles of sequential albumin paclitaxel (125 mg/m2, d1, d8) and carboplatin (AUC=6, d1, Q3W) for 4 cycles. Postoperative completion of 9 cycles of immunotherapy was continued ± the need for postoperative adjuvant radiotherapy was confirmed based on the patient's preoperative status.
Treatment groups
51 Participants
are divided into 1 treatment groupGroup A: TNBC patientsExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Complete pathologic remission (pCR) rate
pCR is defined as ypT0/Tis and ypN0
Time frame
Up to the 30 weeksSecondary outcomes
1
Objective response rate
Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.
Time frame
Up to the 30 weeks2
EFS
Event free survival
Time frame
Up to 12 months after surgery3
Quality of life assessment
Using the EORTC QLQ-BR2. It is based on the core cancer scale EORTCQLQ1-C30 with 23 additional scales specific to breast cancer patients. The questions are specified in the QLQ1C30, and by summing all the questions, a score (0-100) is obtained that is positively related to the quality of life of breast cancer patients.
Time frame
Up to 12 months after surgerySponsors and contacts
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Source ClinicalTrials.gov