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

• ClinicalTrials.gov Identifier: NCT03927456
• Recruitment Status: Unknown
• First Posted: April 25, 2019
• Last Update Posted: June 3, 2021
• Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Information provided by (Responsible Party): Jiangsu HengRui Medicine Co., Ltd.

Tracking Information

• First Submitted Date: April 17, 2019
• First Posted Date: April 25, 2019
• Last Update Posted Date: June 3, 2021
• Actual Study Start Date: June 13, 2019
• Estimated Primary Completion Date: December 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 24, 2019)

Investigator-assessed PFS [ Time Frame: Up to approximately 24 months. ]

Investigator-assessed Progression Free Survival

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 24, 2019)

• Progression-free Survival (PFS) per RECIST 1.1 [ Time Frame: Up to approximately 24 months. ]
  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.
• OS [ Time Frame: Up to approximately 2 years ]
  Overall Survival
• ORR [ Time Frame: Up to approximately 24 months. ]
  Objective Response Rate
• DoR [ Time Frame: Up to approximately 24 months ]
  Duration of Objective Response
• CBR [ Time Frame: Up to approximately 24 months. ]
  Clinical Benefit rate
• AEs and SAEs [ Time Frame: Up to approximately 24 months. ]
  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.
• Ctrough [ Time Frame: Up to 4 weeks ]
  Ctrough

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of SHR6390 in Combination With Fulvestrant in Patients With HR Positive and HER2 Negative Advanced Breast Cancer
• Official Title: A Phase III Study to Evaluate the Efficacy and Safety of SHR6390 in Combination With Fulvestrant Versus Placebo Combined With Fulvesrant in Patients With HR Positive and HER2 Negative Recurrent/Metastatic Breast Cancer
• Brief Summary: This is a phase III clinical trial to evaluate the efficacy and safety of SHR6390 in combination with Fulvestrant versus placebo combined with Fulvesrant in Patients who have HR positive and HER2 negative recurrent/metastatic breast cancer and have received prior endocrine therapy are eligible for study.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Advanced Breast Cancer

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
• Drug: Placebo
  Placebo 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment
• Drug: Fulvestrant
  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

Study Arms

• Experimental: SHR6390 + Fulvestrant
  Intervention Drug: SHR6390, Fulvestrant
  Interventions:

  • Drug: SHR6390
  • Drug: Fulvestrant
• Placebo Comparator: Placebo + Fulvestrant
  Intervention Drug: Placebo, Fulvestrant
  Interventions:

  • Drug: Placebo
  • Drug: Fulvestrant

Publications *

• Liu YP, Hu MH, Lin PP, Li T, Liu SQ, Wang YY, Li SR, Li XK, Wang CJ, Cao Y. Evaluation of the Effect of Food on the Pharmacokinetics of SHR6390, An Oral CDK4/6 Inhibitor, in Healthy Volunteers. Drugs R D. 2022 Jun;22(2):175-182. doi: 10.1007/s40268-022-00390-7. Epub 2022 May 30.
• Xu B, Zhang Q, Zhang P, Hu X, Li W, Tong Z, Sun T, Teng Y, Wu X, Ouyang Q, Yan X, Cheng J, Liu Q, Feng J, Wang X, Yin Y, Shi Y, Pan Y, Wang Y, Xie W, Yan M, Liu Y, Yan P, Wu F, Zhu X, Zou J; DAWNA-1 Study Consortium. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial. Nat Med. 2021 Nov;27(11):1904-1909. doi: 10.1038/s41591-021-01562-9. Epub 2021 Nov 4.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 31, 2021): 357
• Original Estimated Enrollment (submitted: April 24, 2019): 288
• Estimated Study Completion Date: December 30, 2022
• Estimated Primary Completion Date: December 30, 2021 (Final data collection date for primary outcome measure)

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 or prepostmenopausal women
3. Received prior endocrine therapy
4. One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy.
5. Eastern Cooperative Oncology Group [ECOG] 0-1

Exclusion Criteria:

1. Patients who received prior treatment with any CDK4/6 inhibitor, everolimus or fulvestant.
2. 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03927456
• Other Study ID Numbers: SHR6390-III-301
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Jiangsu HengRui Medicine Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Jiangsu HengRui Medicine Co., Ltd.
• Verification Date: June 2020