Neoadjuvant With Trastuzumab, Pyrotinib Plus Palbociclib and Fulvestrant in HER2-positive, ER-positive Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Palbociclib
- Conditions
- Estrogen Receptor-positive Breast Cancer
- Sponsor
- Fudan University
- Enrollment
- 37
- Locations
- 1
- Primary Endpoint
- pathological complete response (pCR)
- Status
- Recruiting
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a prospective Single-arm Study to Investigate the Efficacy and Safety of Neoadjuvant treatment with trastuzumab and pyrotinib plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer.
Detailed Description
ER+HER2+ breast cancer have low response to single endocrine therapy, however the efficacy was improved when treated with endocrine therapy combined with anti-HER2 target therapy. Palbociclib, to be a CDK4/6 inhibitor, has synergistic with tamoxifen and trastuzumab in ER+/HER2+ cells. In China, there is nearly 40000 new patients with ER+/HER2+ breast cancer every year. The encouraging results in NA-PHER2 study suggested the triple targeting of ER, HER2, and RB1 could be an effective chemotherapy-free treatment strategy in neoadjuvant therapy. However, pertuzumab is very expensive. The investigators plan to replace pertuzumab with pyrotinib. Pyrotinib, a new irreversible pan-Her inhibitor in China pharmaceutical company. The objective is to evaluate the efficacy and safety of Neoadjuvant treatment with trastuzumab and pyrotinib plus palbociclib and fulvestrant (TPPF) in this target population. 37 patients will enter the single-arm treatment group. The participants will receive an association of drugs (trastuzumab, pyrotinib, palbociclib plus Fulvestrant, TPPF) as neoadjuvant therapy. Surgery will be performed not earlier than 14 days and not later than 28 days after the last dose of any of the drugs in the combination. The primary endpoint is the rate of pathological complete response (pCR) defined as ypT0-ypTis ypN0 at surgery. The secondary endpoint include the change in Ki67 expression from baseline and at C2D15 of treatment and at surgery, objective response rate and safety.
Investigators
Zhimin Shao
Professor
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Age: 18 or older than 18;
- •Postmenopausal; Pre-menopausal and peri-menopausal female patients must receive ovarian function inhibitors or ovariectomy concurrently.
- •Have not received chemotherapy or endocrine therapy in the past;
- •Have been confirmed as breast invasive ductal carcinoma by the imaging examination and pathological biopsy;
- •Patients with locally advanced breast cancer, stage IIa-IIIa
- •HER2 status to be centrally confirmed (HER2 3+ of neu amplified)
- •Positive estrogen receptor (ER) \> 10%
- •Estimated survival \> 12 months;
- •ECOG physical status score before treatment is 0-1 points;
- •The patient has a measurable lesion (according to the standard RECIST 1.1);
Exclusion Criteria
- •Have performed any local or systemic treatment (including chemotherapy, radiotherapy, targeted drug therapy, experimental treatment, etc.) for the breast cancer;
- •Inflammatory breast cancer, bilateral breast cancer or breast cancer with distant metastasis found;
- •Subjects with uncontrolled lung disease, severe infection, active gastrointestinal ulcer, coagulopathy, severe uncontrolled diabetes, connective tissue disease or inhibition of bone marrow function who cannot tolerate neoadjuvant therapy and related therapy;
- •Peripheral neuropathy caused by any factor \> 1 degree;
- •Subjects who previously have a history of congestive heart failure, uncontrolled or symptomatic angina, arrhythmia or myocardial infarction, and uncontrollable hypertension (systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 100 mmHg);
- •Previous extensive radiotherapy
- •Current use or anticipated need for food or drugs that are known strong CYP3A4 (cytochrome P450 3A4) inhibitors or inducers.
- •Strong CYP3A inhibitors, including, boceprevir, clarithromycin, conivaptan, delavirdine, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, suboxone, telaprevir, telithromycin, voriconazole, and grapefruit, grapefruit juice or any product containing grapefruit.
- •Strong CYP3A inducers, including carbamazepine, phenytoin, primidone, rifampin, rifapentin, and St. John's wort.
- •Breast cancer during the lactation period and gestation period;
Arms & Interventions
TPPF group
Patients will be treated with Trastuzumab, Pyrotinib, Palbociclib plus Fulvestrant(TPPF).
Intervention: Palbociclib
TPPF group
Patients will be treated with Trastuzumab, Pyrotinib, Palbociclib plus Fulvestrant(TPPF).
Intervention: trastuzumab
TPPF group
Patients will be treated with Trastuzumab, Pyrotinib, Palbociclib plus Fulvestrant(TPPF).
Intervention: pyrotinib
TPPF group
Patients will be treated with Trastuzumab, Pyrotinib, Palbociclib plus Fulvestrant(TPPF).
Intervention: fulvestrant
Outcomes
Primary Outcomes
pathological complete response (pCR)
Time Frame: Immediately after the surgery,through study completion, an average of 1 year
Defined as the absence of any invasive cancer cells in the resected breast specimen and all resected lymph nodes following the completion of neoadjuvant therapy. If there is only carcinoma in situ remains, it can be regarded as pCR.
Secondary Outcomes
- changes of Ki67(through study completion, an average of 1 year)
- objective response rate (ORR)(at the end of the combination treatment, up to 1 year)