Ignite Creation Date:
2024-05-06 @ 4:07 PM
Last Modification Date:
2024-10-26 @ 2:03 PM
Study NCT ID:
NCT04872985
Status:
RECRUITING
Last Update Posted:
2021-05-05
First Post:
2021-04-29
Brief Title:
Pyrotinib in Combination With Neoadjuvant Chemotherapy in HRHER2- HER4 High Expression Breast Cancer Patients A Phase II Trial
Sponsor:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Organization:
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study Overview
Official Title:
Efficacy and Safety of Pyrotinib in Combination With Neoadjuvant Chemotherapy in Stage II-III HRHER2- HER4 High Expression Breast Cancer Patients A Phase II Single-center Randomized Double-Blinded Placebo-Controlled Trial
Status:
RECRUITING
Status Verified Date:
2021-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a Phase II single-center double-blind placebo-controlled randomized study of Pyrotinib in combination with DoxorubicinEpirubicin and Cyclophosphamide followed by Docetaxelnab-Paclitaxel as neoadjuvant therapy for women with hormone receptor positive HER2-negative stage II to III breast cancer Patients randomized to the study armcontrol arm will receive standard neoadjuvant chemotherapy in combination with pyrotinibplacebo 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 rateORR event-free survival overall survival and toxicity We will also explore potential prognostic and predictive biomarkers
Detailed Description:
Pyrotinib is an oral irreversible pan-ErbB receptor tyrosine kinase inhibitor TKI with activity against epidermal growth factor receptor HER1EGFR HER2 and HER4 Improvement of the chemotherapy efficacy and good tolerability have been shown by several stage II and III clinical trials in both the neoadjuvant and metastasis setting in HER2-positive breast cancers Yet the anti-tumor effect of Pyrotinib by targeting HER4 has not been determined Preclinical studies show that HER4 is relatively highly expressed in hormone receptor positive and HER2-negativeHRHER2- breast cancers In MCF7 cell lines Pyrotinib effectively repressed phosphorylation of MAPK and Akt signal transduction pathways to inhibit tumor cell proliferation In HRHER2- tumor xenografts Pyrotinib has been observed to inhibit tumor growth in a dose-dependent mannerunpublished data Taken together the data support the rationale that Pyrotinib may be efficacious in HER4 high expressed HRHER2- breast cancer and in combination with chemotherapy may lead to a better pCR rate in the neoadjuvant setting
The study is a two-arm design with a 11 allocation ratio equal numbers of patients randomized to Arms 1 2 The sample size will be up to 140 patients with about 70 evaluable patients in each arm Accrual is expected to occur over 24 months Patients will be randomized to one of the two neoadjuvant therapy regimens Patients in Arm 1 will be assigned to receive 400 mg Pyrotinib orally once per day with four cycles of epirubicin 100 mgm2 or doxorubicin hydrochloride liposome injection 30mgm2 and cyclophosphamide 600 mgm2 intravenously once every 3 weeks followed by four cycles of docetaxel 100 mgm2 intravenously once every 3 weeksor 12 cycles of weekly nab-paclitaxel 120 mgm2 Dosage reduction of pyrotinib is permitted from 400 mg to 320 mg or 240 mg if Pyrotinib-related AEs are experienced In Arm 2 control Pyrotinib will be replaced by 400mg placebo provided by the same pharmacy company
In all arms clinical response will be evaluated by breast MRI The primary endpoint will be assessed with the paraffin embedded pathological specimens collected from surgery Submission of tumor samples for the correlative science studies will be optional for all patients For patients who agree pathological sections of core biopsy specimen before treatment after the patient has signed the consent form and has been screened for eligibility and pathological sections of surgery residual disease specimen after the completion of the treatment are collected In addition a blood sample collected after randomization before the start of study therapy and after the completion of the neoadjuvant therapy will also be required for the correlative studies
The study is a two-arm design with a 11 allocation ratio equal numbers of patients randomized to Arms 1 2 The sample size will be up to 140 patients with about 70 evaluable patients in each arm Accrual is expected to occur over 24 months Patients will be randomized to one of the two neoadjuvant therapy regimens Patients in Arm 1 will be assigned to receive 400 mg Pyrotinib orally once per day with four cycles of epirubicin 100 mgm2 or doxorubicin hydrochloride liposome injection 30mgm2 and cyclophosphamide 600 mgm2 intravenously once every 3 weeks followed by four cycles of docetaxel 100 mgm2 intravenously once every 3 weeksor 12 cycles of weekly nab-paclitaxel 120 mgm2 Dosage reduction of pyrotinib is permitted from 400 mg to 320 mg or 240 mg if Pyrotinib-related AEs are experienced In Arm 2 control Pyrotinib will be replaced by 400mg placebo provided by the same pharmacy company
In all arms clinical response will be evaluated by breast MRI The primary endpoint will be assessed with the paraffin embedded pathological specimens collected from surgery Submission of tumor samples for the correlative science studies will be optional for all patients For patients who agree pathological sections of core biopsy specimen before treatment after the patient has signed the consent form and has been screened for eligibility and pathological sections of surgery residual disease specimen after the completion of the treatment are collected In addition a blood sample collected after randomization before the start of study therapy and after the completion of the neoadjuvant therapy will also be required for the correlative studies
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None