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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: A; Drug: B; Drug: CH1; Drug: CH2; Drug: CL1; Drug: CL2; Drug: CLH1; Drug: CLH2; Drug: CT1; Drug: CL4; Drug: CL3; Drug: CT2; Drug: CT3; Drug: CT4

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhimin Shao, MD.PhD.; Phone Number: 18017312288; Email: zhimingshao@yahoo.com

Study Locations

• China
  • Shanghai, China, 200032
    • Recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Zhimin Shao, PhD; Email: zhimingshao@yahoo.com
  • Please Select
    • Shanghai, Please Select, China, 200032
      • Recruiting
      • Shao Zhimin

Participation Criteria

Eligibility Criteria

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

Description

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

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

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; 6 cycles of Paclitaxel,Carboplatin, Herceptin and Pertuzumab treatment with a good clinical benefit response depending on HR/HER-2 status.	Drug: A; 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.
Experimental: B; 2 cycles of Paclitaxel,Carboplatin, Herceptin treatment with a good clinical benefit response depending on HR/HER-2 status following surgery	Drug: B; 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.
Experimental: CL1; If patients were HR+ and HER2- without PI3K-AKT pathway mutation	Drug: CL1; Drug: SHR6390（CDK4/6 inhibitor）125 mg qd(three week on one week off) oral letrozole 2.5 mg daily； Premenopause：Goserelin 3.6mg IM IM Q4W.
Experimental: CL2; If patients were HR+ and HER2- with PI3K-AKT pathway mutation	Drug: CL2; Drug: SHR6390（CDK4/6 inhibitor）125 mg qd(three week on one week off); Alpelisib 300mg PO QD； Premenopause：Goserelin 3.6mg IM IM Q4W.
Experimental: CLH1; If patients were HR+ and HER2+ without PI3K-AKT pathway mutation	Drug: CLH1; Drug: SHR6390（CDK4/6 inhibitor）125 mg qd(three week on one week off) oral letrozole 2.5 mg daily； 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.
Experimental: CLH2; If patients were HR+ and HER2+ with PI3K-AKT pathway mutation	Drug: CLH2; Drug: oral letrozole 2.5 mg daily; 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.
Experimental: CH1; If patients were HR- and HER2+ without PI3K-AKT pathway mutation	Drug: CH1; 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)
Experimental: CH2; If patients were HR- and HER2+ with PI3K-AKT pathway mutation	Drug: CH2; 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.
Experimental: CT1; If patients were HR- and HER2- with LAR subtype	Drug: CT1; Drug: SHR6390（CDK4/6 inhibitor）125 mg po.qd(three week on one week off) SHR3680（AR inhibitor）240 mg po. qd.
Experimental: CL4; HR+ and HER2-; No correlated pathway variation	Drug: CL4; SHR6390（CDK4/6 inhibitor）125 mg qd(three week on one week off); oral letrozole 2.5 mg daily； Adebrelimab was given intravenously, 600mg each time, once every 2 weeks; Premenopause：Goserelin 3.6mg IM IM Q4W.
Experimental: CL3; HR+ and HER2-; No correlated pathway variation	Drug: CL3; Famitinib 20mg orally once daily; Albumin paclitaxel 100mg/ m2, i.v.; Combined carboplatin AUC=2, i.v.; d1, 8, 15,21 days a cycle, a total of 4 cycles.
Experimental: CT2; TNBC	Drug: CT2; Famitinib 20mg orally once daily; Albumin paclitaxel 100mg/ m2, i.v.; Combined carboplatin AUC=2, i.v.; d1, 8, 15,21 days a cycle, a total of 4 cycles.
Experimental: CT3; TNBC with Homologous Recombination Repair Defect (HRD)	Drug: CT3; Fluzoparil 150mg orally twice daily; Famitinib 20mg orally once daily;
Experimental: CT4; TNBC CD8≥10%	Drug: CT4; Adebrelimab was administered intravenously, 600mg each time, once every 2 weeks; Famitinib 20mg once daily; Albumin paclitaxel 100mg/m2 qw intravenous drip (used for 3 weeks/stopped for 1 week), 28 days per treatment cycle;

What is the study measuring?

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.	through study completion, up to 24 weeks

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.	up to 24 weeks

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: December 29, 2019
• First Submitted That Met QC Criteria: December 29, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; umbrella trial; neo-adjuvant therapy; molecular pathway
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: SCHBCC0N026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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