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 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

Clinical Trial IDs

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

Conditions

  • Advanced Breast Cancer

Interventions

DrugSynonymsArms
SHR6390Cohort 1 (Part 1)
Letrozole or anastrozole or FulvestrantCohort 1 (Part 1)

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1 (Part 1)ExperimentalParticipants receive SHR6390 (at protocol defined dose levels) in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
  • SHR6390
  • Letrozole or anastrozole or Fulvestrant
Cohort 2 (Part 1)ExperimentalSHR6390 (TBD), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
  • SHR6390
  • Letrozole or anastrozole or Fulvestrant
SHR6390 + Letrozole or anastrozole (Part 2)ExperimentalSHR6390 (RP2D, recommended Phase 2 dose), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
  • SHR6390
  • Letrozole or anastrozole or Fulvestrant
SHR6390 + Fulvestrant Cohort 3 (Part 1)ExperimentalSHR6390 (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
  • SHR6390
  • Letrozole or anastrozole or Fulvestrant
SHR6390 + Fulvestrant Cohort 4 (Part 1)ExperimentalSHR6390 (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
  • SHR6390
  • Letrozole or anastrozole or Fulvestrant

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.
      
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
  • Premenopausal women

Last Updated

March 26, 2019