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

Advanced Breast Cancer Clinical Trial

Official title:

A Phase IB/II to Evaluate Efficacy and Safety of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03481998
• Other study ID #: SHR6390-Ib/II-201
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 22, 2018
• Est. completion date: July 30, 2022

Study information

• Verified date: November 2023
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: July 30, 2022
• Est. primary completion date: July 30, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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. Inclusion Criteria

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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms

Intervention

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
• 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

Locations

Country	Name	City	State
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing
China	Ha'erbin Tumor Hospital	Ha'erbin	Heilongjiang
China	Sir Run Run Shaw Hospital of Zhejiang University	Hangzhou	Zhejiang
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With adverse events (AEs) and serious adverse events (SAEs) at Phase 1	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.; Up to 24 months.	Up to 4 weeks
Secondary	Area under the plasma concentration versus time curve (AUC) of SHR6390		Up to 4 weeks
Secondary	Peak Plasma Concentration (Cmax) of SHR6390		Up to 4 weeks
Secondary	The time of SHR6390 to reach the maximum concentration (Tmax)		Up to 4 weeks
Secondary	Half-time (t1/2) of SHR6390		Up to 4 weeks
Secondary	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ¡Ý30% decrease in the sum of diameters of target lesions) per RECIST 1.1.	Up to approximately 24 months.
Secondary	Progression-free Survival (PFS) per RECIST 1.1	PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review or death due to any cause, whichever occurs first.	Up to approximately 24 months.
Secondary	Disease Control Rate (DCR) per RECIST 1.1	DCR is defined as the percentage of participants in the analysis population who have a CR, PR or SD per RECIST 1.1.	Up to approximately 24 months.
Secondary	Number of Participants With adverse events (AEs) and serious adverse events (SAEs)	Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.	Up to approximately 24 months.