Pyrotinib in Combination With Neoadjuvant Chemotherapy in HR+/HER2- HER4 High Expression Breast Cancer Patients: A Phase II Trial
-
- STATUS
- Recruiting
-
- End date
- Dec 31, 2028
-
- participants needed
- 140
-
- sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Summary
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.
Description
Pyrotinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor (TKI) with activity against epidermal growth factor receptor HER1(EGFR), 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-negative(HR+/HER2-) breast cancers. In MCF7 cell lines, Pyrotinib effectively repressed phosphorylation of MAPK and Akt signal transduction pathways to inhibit tumor cell proliferation. In HR+/HER2- tumor xenografts, Pyrotinib has been observed to inhibit tumor growth in a dose-dependent manner(unpublished data). Taken together, the data support the rationale that Pyrotinib may be efficacious in HER4 high expressed HR+/HER2- 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 1:1 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 mg/m2) (or doxorubicin hydrochloride liposome injection 30mg/m2) and cyclophosphamide (600 mg/m2) intravenously, once every 3 weeks, followed by four cycles of docetaxel (100 mg/m2) intravenously, once every 3 weeks(or 12 cycles of weekly nab-paclitaxel 120 mg/m2) . 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.
Details
| Condition | Breast Cancer, Breast Cancer, Breast Cancer Diagnosis, Hormone Receptor Positive Breast Cancer, breast carcinoma, cancer, breast |
|---|---|
| Treatment | cyclophosphamide, docetaxel, Placebo, Epirubicin, Pyrotinib, doxorubicin hydrochloride liposome injection, nab paclitaxel |
| Clinical Study Identifier | NCT04872985 |
| Sponsor | Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University |
| Last Modified on | 12 May 2021 |
How to participate?
,
You have contacted , on
Your message has been sent to the study team at ,
What happens next?
- You can expect the study team to contact you via email or phone in the next few days.
- Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.
You are contacting
Primary Contact
Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.
Learn moreIf you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
Learn moreComplete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.
Learn moreSimilar trials to consider
Not finding what you're looking for?
Sign up as a volunteer to stay informed
Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.
Sign up as volunteer