Clinical Trials /

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

NCT03481998

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of SHR6390 + Letrozole for First-Line Treatment of Postmenopausal Women With HR+/HER2- Advanced Breast Cancer
  • Official Title: Phase 1b/2, Open-label Study of the Safety, Efficacy and Pharmacokinetics of Letrozole Plus SHR6390 (Oral CDK4/6 Inhibitor) For the First-line Treatment of HR Positive, HER2 Negative Advanced Breast Cancer in Postmenopausal Women

Clinical Trial IDs

  • ORG STUDY ID: SHR6390-Ib/II-201
  • NCT ID: NCT03481998

Conditions

  • Advanced Breast Cancer

Interventions

DrugSynonymsArms
SHR6390Cohort 1 (Part 1)
LetrozoleCohort 1 (Part 1)

Purpose

The Study is aimed to evaluate the safety SHR6390 plus Letrozole and to assess the effect of the combination on Advanced Breast Cancer

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 (Part 1)ExperimentalParticipants receive SHR6390 (at protocol defined dose levels) in combination with letrozole 2.5 mg, orally once daily (continuously).
  • SHR6390
  • Letrozole
Cohort 2 (Part 1)ExperimentalSHR6390 (TBD), in combination with letrozole 2.5 mg, orally once daily (continuously).
  • SHR6390
  • Letrozole
SHR6390 + Letrozole (Part 2)ExperimentalSHR6390 (RP2D, recommended Phase 2 dose), in combination with letrozole 2.5 mg, orally once daily (continuously).
  • SHR6390
  • Letrozole

Eligibility Criteria

        Inclusion Criteria:

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

          -  Age: 18 - 75 years old, postmenopausal women.

          -  No prior systemic anti-cancer therapy for advanced HR+ disease.

          -  Eastern Cooperative Oncology Group [ECOG] 0-1

          -  Measurable disease as per Response Evaluation Criterion in Solid Tumors [RECIST] 1.1

          -  Adequate organ and marrow function

        Exclusion Criteria:

          -  Confirmed diagnosis of HER2 positive disease

          -  Patients who received Non-steroidal aromatase inhibitors (letrozole or anastrozole) as
             neo/adjuvant therapy for breast cancer are eligible. If the prior neo/adjuvant therapy
             included letrozole or anastrozole, the disease-free interval must be greater than 12
             months from the completion of treatment until study entry.

          -  Patients who received prior treatment with any CDK4/6 inhibitor.

          -  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.

          -  Has known active central nervous system metastases.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With adverse events (AEs) and serious adverse events (SAEs) at Phase 1
Time Frame:Up to 4 weeks
Safety Issue:
Description:Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03. Up to 24 months.

Secondary Outcome Measures

Measure:Area under the plasma concentration versus time curve (AUC) of SHR6390
Time Frame:Up to 4 weeks
Safety Issue:
Description:
Measure:Peak Plasma Concentration (Cmax) of SHR6390
Time Frame:Up to 4 weeks
Safety Issue:
Description:
Measure:The time of SHR6390 to reach the maximum concentration (Tmax)
Time Frame:Up to 4 weeks
Safety Issue:
Description:
Measure:Half-time (t1/2) of SHR6390
Time Frame:Up to 4 weeks
Safety Issue:
Description:
Measure:Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame:Up to approximately 24 months.
Safety Issue:
Description: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.
Measure:Progression-free Survival (PFS) per RECIST 1.1
Time Frame:Up to approximately 24 months.
Safety Issue:
Description: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.
Measure:Disease Control Rate (DCR) per RECIST 1.1
Time Frame:Up to approximately 24 months.
Safety Issue:
Description:DCR is defined as the percentage of participants in the analysis population who have a CR, PR or SD per RECIST 1.1.
Measure:Number of Participants With adverse events (AEs) and serious adverse events (SAEs)
Time Frame:Up to approximately 24 months.
Safety Issue:
Description:Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Jiangsu HengRui Medicine Co., Ltd.

Trial Keywords

  • CDK4/6 inhibitor
  • Breast cancer
  • Postmenopausal women
  • Hormone-receptor positive
  • HER2 negative

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