Breast Cancer Clinical Trial
Official title:
Efficacy and Safety of Pyrotinib in Combination With Neoadjuvant Chemotherapy in Stage II-III HR+/HER2-, HER4 High Expression Breast Cancer Patients: A Phase II, Single-center, Randomized, Double-Blinded, Placebo-Controlled Trial
This is a Phase II, single-center, double-blind, placebo-controlled, randomized study of Pyrotinib in combination with Doxorubicin/Epirubicin and Cyclophosphamide followed by Docetaxel/nab-Paclitaxel as neoadjuvant therapy for women with hormone receptor positive HER2-negative stage II to III breast cancer. Patients randomized to the study arm/control arm will receive standard neoadjuvant chemotherapy in combination with pyrotinib/placebo, respectively. The primary endpoint of the study is the total pathological complete response (pCR) rate. Secondary endpoints include the pCR rate in breast only, objective response rate(ORR), event-free survival, overall survival, and toxicity. We will also explore potential prognostic and predictive biomarkers.
Status | Recruiting |
Enrollment | 140 |
Est. completion date | December 31, 2028 |
Est. primary completion date | December 31, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility | Inclusion Criteria: - Presenting with histological(by core needle biopsy or by limited incisional biopsy) proven hormone receptor positive (ER=10% and/or PR =1%), HER2 negative(IHC =2+ and/or FISH-) , stage II/ III breast cancer. - Have clinical indication for neoadjuvant therapy. - HER4 IHC score = 4. - Measurable disease (breast and/or lymph nodes). - The Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1. - Adequate bone marrow function (within 4 weeks prior to registration): WBC=3.0x109/l, neutrophils =1.5 x 109/l, platelets =100 x 109/l. - Adequate liver function (within 4 weeks prior to registration): bilirubin =1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT =2.5 x UNL, Alkaline Phosphatase =5 x UNL. - Adequate renal function (within 4 weeks prior to registration): the calculated creatinine clearance should be =50 ml/min. - Patients must have the ability to swallow oral medication. - Without history of any kind of treatment to known malignancy (solid tumor or hematologic). - Written informed consent. - Accessible for treatment and follow-up. Exclusion Criteria: - Evidence of stage IV breast cancer. - Contralateral invasive breast cancer or Inflammatory breast cancer. - History of non-breast malignancies (except for in situ cancers treated only by local excision and basal cell and squamous cell carcinomas of the skin) within 5 years prior to randomization. - Known metastatic disease from any malignancy (solid tumor or hematologic). - Serious other diseases as infections (hepatitis B, C and HIV), recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias or on screening, any of the following cardiac parameters: bradycardia (heart rate <50 at rest) or QTcF =450 msec. - Known hypersensitivity reaction to any of the components of the treatment. - Pregnancy or lactation at the time of randomization. - Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent. |
Country | Name | City | State |
---|---|---|---|
China | Sun-Yat-Sen Memorial Hospital of Sun-Yat-Sen University | Guangzhou | Guangdong |
Lead Sponsor | Collaborator |
---|---|
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Jiangsu HengRui Medicine Co., Ltd. |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | tpCR (total pCR) | ypT0/isN0, number of participants with by no histologic evidence of invasive tumor cells in the surgical breast and axillary specimen. | At the time of surgery. | |
Secondary | pCR of the breast | ypT0/is, number of participants with by no histologic evidence of invasive tumor cells in the surgical breast specimen. | At the time of surgery. | |
Secondary | ORR (objective response rate) | the percentage of patients with a final overall response of CR or PR relative to the appropriate analysis set. Clinical response will be evaluated by breast MRI. | At the time of surgery. | |
Secondary | EFS (event-free survival) at 3 and 5 years | EFS is defined as the time from randomization to the date of progression(according to RECIST 1.1 ) of disease that precludes surgery, local relapse, regional relapse, distant relapse, second primary invasive breast cancer including contralateral breast cancer, or death due to any cause which ever occurred first. | EFS will be determined at 3 and 5 years after randomization | |
Secondary | OS (overall survival) at 3 and 5 years | OS is defined as the time from randomization to date of death. | OS will be determined at 3 and 5 years after randomization | |
Secondary | Exploring potential biomarkers as predictors of tpCR, pCR of the breast and ORR. | We will used immunohistochemistry (IHC) method to assess the positive percentage of ER, PR, Ki67%, as well as the HER4 scores, and the status EGFR, HER3, and PD-L1 of the specimen from primary core biopsy at baseline. The IHC4 score will be calculated using our modified method (Jin et al. Oncologist. 2020 Aug;25(8):e1170-e1180.). The association between these biomarkers with tpCR, pCR of the breast and ORR will be explored. The association between these biomarkers with the benefit of adding pyrotinib to neoadjuvant chemotherapy (interaction/effect modification effects) will also be explored. | The correlation with pCR will be assessed when the surgery is performed on the last enrolled patients. | |
Secondary | Exploring potential biomarkers as predictors of EFS and OS. | We will used immunohistochemistry (IHC) method to assess the positive percentage of ER, PR, Ki67%, as well as the HER4 scores, and the status EGFR, HER3, and PD-L1 of the specimen from primary core biopsy at baseline, as well as the residual surgical specimen after neoadjuvant chemotherapy. The IHC4 score will be calculated using our modified method (Jin et al. Oncologist. 2020 Aug;25(8):e1170-e1180.). The association between these biomarkers with EFS and OS will be explored. The association between these biomarkers with the benefit of adding pyrotinib to neoadjuvant chemotherapy (interaction/effect modification effects) will also be explored. | The association with EFS and OS will be performed at 5 years after the enrollment of the last patient. | |
Secondary | Toxicity according to NCI CTCAE v4.03 all grades and grade III/IV. | Toxicities are graded according to NCI CTCAE v4.03. | Toxicity will be assessed from start treatment up to 30 days following the last dose of treatment. | |
Secondary | Exploring the association between NGS sequencing and ctDNA data with clinical outcomes(Optional). | NGS sequencing will be performed with the pathological section of primary core biopsy and surgery residual specimen, and the ctDNA will be extracted from the patients' serum at baseline and the date of surgery, if with the agreement of participants. The association between these biomarkers with clinical outcomes (pCR and EFS) will be assessed when possible. | The correlation with pCR will be assessed when the surgery is performed on the last enrolled patients. The association with EFS and OS will be performed at 5 years after the enrollment of the last patient. |
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