A Study of Neoadjuvant SHR6390 in Combination With Anastrozole, Pyrotinib, and Trastuzumab in Patients With ER+/HER2+ Breast Cancer.

Phase 2

• Conditions: Breast Cancer; HER2-positive Breast Cancer; ER-positive Breast Cancer
• Interventions: Drug: SHR6390; Drug: Anastrozole; Drug: Pyrotinib; Drug: Trastuzumab

• Registration Number: NCT04236310
• Lead Sponsor: Ruijin Hospital

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-01
• Study Start: 2020-01-15
• Study First Submitted: 2020-01-17
• Study First Submitted QC: 2020-01-17
• Last Update Submitted: 2020-01-17
• Study First Posted: 2020-01-22
• Last Update Posted: 2020-01-22
• Primary Completion: 2022-12-31
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 37

Inclusion Criteria

1. Written informed consent for all study according to local regulatory requirements prior to beginning specific protocol procedures.
2. Age at diagnosis ≥18 years and ≤75 years, female.
3. 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.
4. Tumor diameter >2 centimeters with the clinical stage being classified as from IIa to IIIc.
5. ECOG ≤ 1, LVEF ≥ 55%.
6. 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

1. Evidence of bilateral invasive breast cancer or metastatic disease (M1).
2. Pevious treatment with chemotherapy, hormonal therapy, an investigational drug for any type of malignancy, or radiation therapy.
3. 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).
4. Known hypersensitivity reaction to one of the compounds or incorporated substances used in this protocol.
5. Active infection or severe symptomatic visceral disease in the last 4 weeks.
6. 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).
7. Prior malignancy with a disease-free survival of < 5 years, except curatively treated basalioma of the skin, pTis of the cervix uteri.
8. Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices, sterilization) during study treatment.
9. Participation in another clinical trial with any investigational, not marketed drug within 30 days prior to study entry.
10. Not eligible for the trial assessed by the investigators of our study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SHR6390+Anastrozole+Pyrotinib+Trastuzumab±Ovarian Suppression	SHR6390	-
SHR6390+Anastrozole+Pyrotinib+Trastuzumab±Ovarian Suppression	Pyrotinib	-
SHR6390+Anastrozole+Pyrotinib+Trastuzumab±Ovarian Suppression	Anastrozole	-
SHR6390+Anastrozole+Pyrotinib+Trastuzumab±Ovarian Suppression	Trastuzumab	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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.
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)