Clinical trial NCT03481998: A Study of SHR6390 in Combination With Letrozole or Anastrozole or Fulvestrant in Patients With HR Positive and HER2 Negative Advanced Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Breast Cancer
Keywords: CDK4/6 inhibitor
Breast cancer
Postmenopausal women
Hormone-receptor positive
HER2 negative
Premenopausal women
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-03-29
Enrollment: 104
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

   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.

Primary outcomes:
measure: Number of Participants With adverse events (AEs) and serious adverse events (SAEs) at Phase 1
timeFrame: Up to 4 weeks
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC) of SHR6390
timeFrame: Up to 4 weeks
measure: Peak Plasma Concentration (Cmax) of SHR6390
timeFrame: Up to 4 weeks
measure: The time of SHR6390 to reach the maximum concentration (Tmax)
timeFrame: Up to 4 weeks
measure: Half-time (t1/2) of SHR6390
timeFrame: Up to 4 weeks
measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Up to approximately 24 months.
measure: Progression-free Survival (PFS) per RECIST 1.1
timeFrame: Up to approximately 24 months.
measure: Disease Control Rate (DCR) per RECIST 1.1
timeFrame: Up to approximately 24 months.
measure: Number of Participants With adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to approximately 24 months.
Other outcomes:
Locations:
city: Ha'erbin
country: China
facility: Ha'erbin Tumor Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital of Zhejiang University
state: Zhejiang
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Binhe Xu, MD
role: PRINCIPAL_INVESTIGATOR
References: