A Study of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Advanced Breast Cancer

NCT ID: NCT03481998

Last Updated: 2023-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-22
• Study Completion Date: 2022-07-30

Brief Summary

This is a phase IB/II clinical trial to evaluate the efficacy and safety of SHR6390 in combination with Letrozole or Anastrozole or Fulvestrant. Patients who have HR positive and HER2 negative recurrent/metastatic breast cancer and have not received systemic anticancer therapy are eligible for study.

Conditions

Advanced Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 (Part 1)

Participants receive SHR6390 (at protocol defined dose levels) in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).

Group Type: EXPERIMENTAL

SHR6390

Intervention Type: DRUG

SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

Letrozole or anastrozole or Fulvestrant

Intervention Type: DRUG

Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease

Cohort 2 (Part 1)

SHR6390 (TBD), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).

Group Type: EXPERIMENTAL

SHR6390

Intervention Type: DRUG

SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

Letrozole or anastrozole or Fulvestrant

Intervention Type: DRUG

Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease

SHR6390 + Letrozole or anastrozole (Part 2)

SHR6390 (RP2D, recommended Phase 2 dose), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).

Group Type: EXPERIMENTAL

SHR6390

Intervention Type: DRUG

SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

Letrozole or anastrozole or Fulvestrant

Intervention Type: DRUG

Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease

SHR6390 + Fulvestrant Cohort 3 (Part 1)

SHR6390 (at protocol defined dose levels), in combination with Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle once daily

Group Type: EXPERIMENTAL

SHR6390

Intervention Type: DRUG

SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

Letrozole or anastrozole or Fulvestrant

Intervention Type: DRUG

Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease

SHR6390 + Fulvestrant Cohort 4 (Part 1)

SHR6390 (TBD), in combination with Fulvestrant 500 mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle once daily

Group Type: EXPERIMENTAL

SHR6390

Intervention Type: DRUG

SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

Letrozole or anastrozole or Fulvestrant

Intervention Type: DRUG

Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease

Interventions

SHR6390

SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

Intervention Type: DRUG

Letrozole or anastrozole or Fulvestrant

Letrozole 2.5mg or anastrozole 1mg, orally once daily (continuously)， or Fulvestrant 500mg intramuscular injection on day 1 and day 15 for the first cycle and then on day 1 for every cycle until progressive disease

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Has the pathologically-confirmed diagnosis of locally recurrent or metastatic, hormone-receptor positive, HER2 negative Breast Cancer.

2. Age: 18 - 75 years old, postmenopausal women.prepostmenopausal women, but should receive Ovary castration.

3. Cohort 1 and Cohort 2 :No prior systemic anti-cancer therapy for advanced HR+ disease.

Cohort 3 and Cohort 4 : Patients must satisfy the following criteria for prior therapy:

1. a) Progressed after 2 years during treatment of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal.

b)Progressed within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre- or perimenopausal.

c) Progressed while 6 month after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer if postmenopausal, or prior endocrine treatment for advanced/metastatic breast cancer if pre- or perimenopausal.

2. One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy.

4. Eastern Cooperative Oncology Group [ECOG] 0-1 Measurable disease as per Response Evaluation Criterion in Solid Tumors[RECIST] 1.1

5. Adequate organ and marrow function

Exclusion Criteria

1. Confirmed diagnosis of HER2 positive disease

2. Patients who received any endocrine therapy as neo/adjuvant therapy for breast cancer are eligible. If the neo/adjuvant therapy of any endocrine therapy , the disease-free interval must be greater than 12 months from the completion of treatment until study entry.

3. Patients who received prior treatment with any CDK4/6 inhibitor, everolimus,fulvestant.

4. Clinically significant cardiovascular and cerebrovascular diseases,including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure (New York heart association (NYHA) class > 2), or ventricular arrhythmia which need medical intervention.

5. Has known active central nervous system metastases.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu HengRui Medicine Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Binhe Xu, MD

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Locations

Ha'erbin Tumor Hospital

Harbin, Heilongjiang, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Sir Run Run Shaw Hospital of Zhejiang University

Hangzhou, Zhejiang, China

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, , China

Countries

China

References

Zhang Q, Zhang P, Yan M, Yan X, Wang X, Gu Y, Qu X, Li S, Xu G, Zhu X, Xu B. Dalpiciclib in combination with letrozole/anastrozole or fulvestrant in HR-positive and HER2-negative advanced breast cancer: results from a phase Ib study. Ther Adv Med Oncol. 2024 Sep 2;16:17588359241273026. doi: 10.1177/17588359241273026. eCollection 2024.

Reference Type: DERIVED

PMID: 39229468 (View on PubMed)

Other Identifiers

SHR6390-Ib/II-201

Identifier Type: -

Identifier Source: org_study_id