SHR6390 Combined With Anastrozole for Preoperative Treatment of Breast Cancer.

Single-arm, Single-center, PhaseⅡ Clinical Study of SHR6390 Combined With Anastrozole for Preoperative Treatment of Hormone Receptor Positive and HER2 Negative Early or Locally Advanced Breast Cancer.

The study is being conducted to assess effect of SHR6390 combined with anastrozole on proliferation of HR-positive HER2-negative breast cancer tumor cells before surgery.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: SHR6390+anatrozole

Detailed Description

This is a single-arm, single-center, open-label Phase II clinical study. The purpose of this study was to evaluate the effect of SHR6390 combined with anastrozole on the proliferative activity of HR-positive HER2-negative breast cancer tumor cells before surgery.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Liu Hong, M.D.; Phone Number: 022-23340123; Email: lh713@163.com

Study Locations

• China
  • Tianjin, China, 300060
    • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1.Female subjects aged 18 to 75 years old, meet any of the following:

1. Both ovaries have been removed, or the age is ≥60 years old;
2. Age <60 years, natural post-menopausal state (defined as spontaneous menstrual cessation for at least 12 consecutive months without other pathological or physiological reasons), E2 and FSH are at postmenopausal levels;
3. Premenopausal or perimenopausal female subjects must be willing to receive LHRH agonist treatment during the study; 2.T2-T4cN0M0 invasive breast cancer (according to the AJCC 8th edition breast cancer clinical staging guidelines), the tumor must be surgically resectable, the measurable lesion conforms to the RECIST 1.1 standard, and the maximum diameter of the primary tumor has been evaluated by clinical or imaging evaluation ≥ 2cm; 3.Willing to accept biopsy; 4.Luminal A confirmed by immunohistochemistry, ER≥50% and PR≥50%; 5.HER2 negative, defined as immunohistochemical test 0/1+; or FISH test HER2/CEP17 ratio is less than 2.0 or HER2 gene copy number is less than 4; 6.Patients are suitable for neoadjuvant therapy and willing to accept (judged by the investigator); 7.ECOG performance status score 0 or 1; 8.The expected survival period is not less than 12 weeks; 9.Adequate function of major organs； 10.Voluntary participation in the study, signed informed consent, good compliance and willingness to cooperate with follow-up.

Exclusion Criteria:

1. Metastases confirmed by imaging or pathology, not including lymph node metastases in the ipsilateral and/or contralateral thoracic region or mediastinum;
2. Inflammatory breast cancer, bilateral breast cancer or DCIS, invasive breast cancer with multiple focal lesions;
3. Previous pathological diagnosis of HER2-positive breast cancer;
4. Suffering from gastrointestinal diseases such as intestinal obstruction, peptic ulcer or active bleeding, which affects the taking and absorption of drugs;
5. Previously treated with radiotherapy, chemotherapy, surgery (not including percutaneous puncture) or molecular targeted treatment;
6. Previously received any CDK4/6 inhibitor drug treatment;
7. Participation in any other clinical trials within 4 weeks of enrollment；
8. Concurrent use of any other Anti-cancer drugs；
9. Other malignancies within 5 years, except cured in-situ of uterine cervix carcinoma , skin basal cell carcinoma and squamous-cell carcinoma;
10. History of heart disease: (1) Arrhythmias requiring medical treatment or clinical significance, (2) Myocardial infarction, (3) Heart failure, (4)Any heart diseases that investigator believes not suitable for this study;
11. History of allergy or hypersensitivity to any of the study drugs or study drug components; history of immunodeficiency including HIV-positive, active hepatitis B/C, other acquired, congenital immunodeficiency disease or history of organ transplantation；
12. A clear history of neurological or mental disorders, including epilepsy or dementia；
13. Pregnant or breastfeeding women. Women of childbearing potential who have a positive pregnancy test or unwilling to use adequate contraception prior to enrollment and for the duration of study participation；
14. According to the investigator's judgment, there is a concomitant disease that seriously endangers the safety of subjects or affects the completion of the study (including but not limited to severe hypertension, severe diabetes, active infection, thyroid disease that cannot be controlled by drugs)；
15. Any condition which in the investigator's opinion makes the subjects unsuitable for the study participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR6390+anatrozole; Hormone receptor positive, HER2 negative participants will receive SHR6390 in combination with anatrozole before surgery.	Drug: SHR6390+anatrozole; SHR6390 is a novel small molecule inhibitor specifically targeting the CDK4/6 pathway.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Ki67 scores	Serial measures of Ki67 (%)	up to 5 months
RCB (0-1) after surgery	Rate of Residual Cancer Burden 0-1	5 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) evaluated by the investigator	ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) according to RECIST 1.1.	16 weeks
tpCR	pCR is defined as the absence of noninvasive tumor residuals in breast and axillary lymph nodes (ypT0/is ypN0) after neoadjuvant therapy.	5 months
Safety will be assessed using NCI Common Terminology Criteria for Adverse Events v5.0 (CTCAE)		6 months

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2021
• Primary Completion (Actual): February 28, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: April 2, 2021
• First Submitted That Met QC Criteria: April 7, 2021
• First Posted (Actual): April 8, 2021

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BC-NEO-IIT-SHR6390

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No