A Study of Neoadjuvant SHR6390 in Combination With Anastrozole, Pyrotinib, and Trastuzumab in Patients With ER+/HER2+ Breast Cancer.
Study Details
Study Description
Brief Summary
To evaluate the efficacy and safety of the SHR6390 in combination with anastrozole, pyrotinib, and trastuzumab in patients with ER-positive, HER2-positive breast cancer in the neoadjuvant setting.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SHR6390+Anastrozole+Pyrotinib+Trastuzumab±Ovarian Suppression
|
Drug: SHR6390
SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment for 4 cycles
Drug: Anastrozole
Anastrozole 1md, orally once daily for 16 weeks (For premenopausal women, ovarian suppression may be considered)
Drug: Pyrotinib
Pyrotinib 400mg once daily for 16 weeks
Drug: Trastuzumab
Trastuzumab 6mg/kg (loading dose, 8mg/kg), infusion once every 3-week cycle for 5 cycles.
|
Outcome Measures
Primary Outcome Measures
- Ki67 changes from baseline to 2 weeks after the start of the neoadjuvant therapy [2 weeks]
Ki67 changes from baseline to at 2 weeks after the start of the neoadjuvant therapy
Secondary Outcome Measures
- Ki67 changes from baseline to at surgery [average 19 weeks after the start of the neoadjuvant therapy]
Ki67 changes from baseline to at surgery
- Pathological complete response (ypT0/is ypN0) rate [average 19 weeks after the start of the neoadjuvant therapy]
Absence of invasive cancer in the breast and axillary nodes, irrespective of ductal carcinoma in situ.
- Objective response rate (ORR) [average 19 weeks after the start of the neoadjuvant therapy]
ORR includes all patients whose cancer has a partial or complete response according to RECIST 1.1
- Invasive disease-free survival (IDFS) [5 years]
IDFS is defined as the time period between registration and first event (ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, death attributable to any cause, contralateral invasive breast cancer, second primary nonbreast invasive cancer)
- Tolerability and safety: number of patients whose treatment had to be reduced, delayed or permanently stopped [during treatment (16 weeks)]
Descriptive statistics will be given on the number of patients whose treatment had to be reduced, delayed or permanently stopped.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures.
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Age at diagnosis ≥18 years and ≤75 years, female.
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Histologically confirmed diagnosis of Unilateral ER+/HER2+ breast cancer. ER-positivity is defined as >1% stained cells；HER2-positivity is defined as IHC 3+ or if IHC scored 2+, in-situ hybridisation (ISH) suggests amplified HER2 gene.
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Tumor diameter >2 centimeters with the clinical stage being classified as from IIa to IIIc.
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ECOG ≤ 1, LVEF ≥ 55%.
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Laboratory requirements: for hematology, absolute neutrophil count (ANC) ≥1.5 × 109 / L and platelets ≥100 × 109 / L and hemoglobin ≥90 g/L; for hepatic function, total bilirubin ≤1.5 × UNL, AST and ALT ≤2.5 × UNL; for renal function, SCr ≤1.5 × UNL.
Exclusion Criteria:
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Evidence of bilateral invasive breast cancer or metastatic disease (M1).
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Pevious treatment with chemotherapy, hormonal therapy, an investigational drug for any type of malignancy, or radiation therapy.
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Any of the following exist in the last 6 months: known or suspected congestive heart failure (≥ NYHA II), persistent arrhythmias (≥ grade 2), atrial fibrillation of any grade, coronary / peripheral bypass, symptomatic congestive heart failure, cerebrovascular accidents (including transient cerebral hemorrhage attacks or symptomatic pulmonary embolism).
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Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol.
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Active infection or severe symptomatic visceral disease in the last 4 weeks.
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Patients with HIV infection or known AIDS, or patients with infection of active hepatitis B (HBV DNA ≥1000IU / ml) or hepatitis C (hepatitis C antibody is positive and HCV RNA is above the lower limit of detection of the analytical method).
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Prior malignancy with a disease-free survival of < 5 years, except curatively treated basalioma of the skin, pTis of the cervix uteri.
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Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
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Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry.
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Not eligible for the trial assessed by the investigators of our study.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Ruijin Hospital
- Jiangsu HengRui Medicine Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RJBC2001