A Clinical Trial of Breast Cancer Neo-adjuvant Therapy Based on Molecular Pathway in FUSCC

Study Overview
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Brief Summary
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This is a Phase Ib/II, prospective , open-label, single center, Bayesian adaptive design, umbrella study evaluating the efficacy and safety of neo-adjuvant therapy in patients with breast cancer.

Official Title
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This is a Phase Ib/II, Prospective , Open-label, Single Center, Bayesian Adaptive Design, Umbrella Study Evaluating the Efficacy and Safety of Neo-adjuvant Therapy in Patients With Breast Cancer.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: A
* Drug: B
* Drug: CL1
* Drug: CL2
* Drug: CLH1
* Drug: CLH2
* Drug: CH1
* Drug: CH2
* Drug: CT1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-70 years old Expected survival > 12 months Baseline ECOG Performance Status rating 0-1 Naïve to chemotherapy or hormonal treatments Radiologically confirmed and biopsy diagnosed invasive ductal carcinoma of breast and prepared to be treated surgically Locally advance breast cancer of stage IIb-IIIc No concurrent malignancy (except controlled cervical carcinoma in situ or basal cell carcinoma of skin) Patients have measurable lesions (according to RECIST v1.1 criteria) Intention to cooperate with baseline puncture and neoadjuvant therapy No advanced metastasis or metastasis involving brain or liver Adequate bone marrow function, blood routine examination shows neutrophil count ≥ 1.5x109/L, hemoglobin level ≥ 100 g/L, Platelets ≥ 100 x 109/L Adequate liver and kidney function, serum aminotransferase (AST) ≤ 60U/L, serum total bilirubin ≤ 2.5 times ULN, serum creatinine ≤110μmol/L, urea nitrogen ≤7.1mmol/L No coagulation abnormality Normal heart function, with normal ECG and LVEF ≥ 55% Women of childbearing age agree to take reliable contraceptive measures during clinical trials, and negative serum or urine pregnancy test within 7 days prior to administration No coagulation abnormality Sign the informed consent statement and voluntarily receive follow-ups, treatments, laboratory tests and other research procedures according to protocol. Exclusion Criteria: Previous regional or systemic treatment for breast cancer (include but not limited to chemotherapy, radiotherapy, targeted therapy, other clinical trials) Inflammatory breast cancer, bilateral breast cancer or breast cancer already with distant metastasis Complicated with uncontrolled lung disease, severe infection, active peptic ulcer, blood clotting disorders, severe uncontrolled diabetes, connective tissue disorders or bone marrow suppression, and intolerance to neoadjuvant therapy or related treatment Peripheral neuropathy >1 degree caused by any reason History of congestive heart failure, uncontrolled or symptomatic angina, arrhythmias or history of myocardial infarction, refractory hypertension (systolic blood pressure > 180 mmHg or diastolic blood pressure > 100 mmHg); Breast cancer during lactation or pregnancy Unwillingly to receive baseline puncture or neoadjuvant therapy Mental illness or incompliance to treatment caused by other reasons Known history of severe hypersusceptibility to any agents used in the treatment protocol Patients received major surgery or suffered from severe trauma within 2 months of first administration Currently enroll or recently used (30 days within enrollment) other agent under research or involved in other trial Known to be infected with human immunodeficiency virus (HIV) Other circumstances considered to be inappropriate to be enrolled by researchers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>6 cycles of Paclitaxel,Carboplatin, Herceptin and Pertuzumab treatment with a good clinical benefit response depending on HR/HER-2 status. | Drug: A<br>* Paclitaxel: paclitaxel 80 mg/m2 ivgtt d1, d8, d15, 28 days per cycle. Carboplatin: carboplatin AUC=2 ivgtt d1, d8, d15, 28 days per cycle. Herceptin: 4 mg/kg (loading dose 8mg/kg) ivgtt d1,8,15, 22, 28 days per cycle,6 cycles. Pertuzumab: 420-mg ( loading dose 840mg) ivgtt d1, 21 days per cycle,6 cycles.<br>|
| Experimental: B<br>2 cycles of Paclitaxel,Carboplatin, Herceptin treatment with a good clinical benefit response depending on HR/HER-2 status following surgery | Drug: B<br>* Paclitaxel: paclitaxel 80 mg/m2 ivgtt d1, d8, d15, 28 days per cycle. Carboplatin: carboplatin AUC=2 ivgtt d1, d8, d15, 28 days per cycle.<br>|
| Experimental: CL1<br>If patients were HR+ and HER2- without PI3K-AKT pathway mutation | Drug: CL1<br>* Drug: SHR6390（CDK4/6 inhibitor）150 mg qd(three week on one week off) Fulvestrant 500mg IM Q4W； Premenopause：Goserelin 3.6mg IM IM Q4W.<br>|
| Experimental: CL2<br>If patients were HR+ and HER2- with PI3K-AKT pathway mutation | Drug: CL2<br>* Drug: SHR6390（CDK4/6 inhibitor）150 mg qd(three week on one week off); Alpelisib 300mg PO QD； Premenopause：Goserelin 3.6mg IM IM Q4W.<br>|
| Experimental: CLH1<br>If patients were HR+ and HER2+ without PI3K-AKT pathway mutation | Drug: CLH1<br>* Drug: SHR6390（CDK4/6 inhibitor）150 mg qd(three week on one week off) Fulvestrant 500mg IM Q4W； Herceptin: 4 mg/kg (loading dose 8mg/kg) ivgtt d1,8,15, 22, 28 days per cycle； Pertuzumab: 420-mg ( loading dose 840mg) ivgtt d1, 21 days per cycle； Premenopause：Goserelin 3.6mg IM IM Q4W.<br>|
| Experimental: CLH2<br>If patients were HR+ and HER2+ with PI3K-AKT pathway mutation | Drug: CLH2<br>* Drug: SHR6390（CDK4/6 inhibitor）150 mg qd (three week on one week off) Alpelisib 300mg PO QD； Herceptin: 4 mg/kg (loading dose 8mg/kg) ivgtt d1,8,15, 22, 28 days per cycle； Pertuzumab: 420-mg ( loading dose 840mg) ivgtt d1, 21 days per cycle； Premenopause：Goserelin 3.6mg IM IM Q4W.<br>|
| Experimental: CH1<br>If patients were HR- and HER2+ without PI3K-AKT pathway mutation | Drug: CH1<br>* Drug: pyrotinib(EGFR-TKI) 400mg qd； Herceptin: 4 mg/kg (loading dose 8mg/kg) ivgtt d1,8,15, 22, 28 days per cycle； capecitabine 1000mg/m2 bid(d1-d14)<br>|
| Experimental: CH2<br>If patients were HR- and HER2+ with PI3K-AKT pathway mutation | Drug: CH2<br>* Drug: Paclitaxel: paclitaxel 80 mg/m2 ivgtt d1, d8, d15, 28 days per cycle. Carboplatin: carboplatin AUC=2 ivgtt d1, d8, d15, 28 days per cycle.Herceptin: 4 mg/kg (loading dose 8mg/kg) ivgtt d1,8,15, 22, 28 days per cycle； Alpelisib 300mg PO QD； Herceptin: 4 mg/kg (loading dose 8mg/kg) ivgtt d1,8,15, 22, 28 days per cycle； Pertuzumab: 420-mg ( loading dose 840mg) ivgtt d1, 21 days per cycle； Premenopause：Goserelin 3.6mg IM IM Q4W.<br>|
| Experimental: CT1<br>If patients were HR- and HER2- with LAR subtype | Drug: CT1<br>* Drug: SHR6390（CDK4/6 inhibitor）150 mg po.qd(three week on one week off) SHR3680（AR inhibitor）240 mg po. qd.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pathologic Complete Response (pCR) | pCR is defined as the absence of noninvasive tumor residuals in breast and axillary lymph nodes (ypT0/is ypN0) after neoadjuvant therapy. | 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, neo-adjuvant therapy, molecular pathway, umbrella trial