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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03481998
Recruitment Status : Active, not recruiting
First Posted : March 29, 2018
Last Update Posted : June 2, 2021
Sponsor:
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Breast Cancer Drug: SHR6390 Drug: Letrozole or anastrozole or Fulvestrant Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 146 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 22, 2018
Estimated Primary Completion Date : December 30, 2021
Estimated Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1 (Part 1)
Participants receive SHR6390 (at protocol defined dose levels) in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
 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: 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
Experimental: Cohort 2 (Part 1)
SHR6390 (TBD), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
 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: 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
Experimental: SHR6390 + Letrozole or anastrozole (Part 2)
SHR6390 (RP2D, recommended Phase 2 dose), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).
 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: 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
Experimental: SHR6390 + Fulvestrant Cohort 3 (Part 1)
SHR6390 (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
 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: 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
Experimental: SHR6390 + Fulvestrant Cohort 4 (Part 1)
SHR6390 (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
 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: 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


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With adverse events (AEs) and serious adverse events (SAEs) at Phase 1 [ Time Frame: Up to 4 weeks ]

    Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.

    Up to 24 months.



Secondary Outcome Measures :
  1. Area under the plasma concentration versus time curve (AUC) of SHR6390 [ Time Frame: Up to 4 weeks ]
  2. Peak Plasma Concentration (Cmax) of SHR6390 [ Time Frame: Up to 4 weeks ]
  3. The time of SHR6390 to reach the maximum concentration (Tmax) [ Time Frame: Up to 4 weeks ]
  4. Half-time (t1/2) of SHR6390 [ Time Frame: Up to 4 weeks ]
  5. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Up to approximately 24 months. ]
    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.

  6. 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.

  7. Disease Control Rate (DCR) per RECIST 1.1 [ Time Frame: Up to approximately 24 months. ]
    DCR is defined as the percentage of participants in the analysis population who have a CR, PR or SD per RECIST 1.1.

  8. Number of Participants With adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to approximately 24 months. ]
    Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03481998


Locations
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China, Heilongjiang
Ha'erbin Tumor Hospital
Ha'erbin, Heilongjiang, China
China, Henan
Henan Cancer Hospital
Zhengzhou, Henan, China, 450008
China, Zhejiang
Sir Run Run Shaw Hospital of Zhejiang University
Hangzhou, Zhejiang, China
China
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, China
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Investigators
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Principal Investigator: Binhe Xu, MD Cancer Institute and Hospital, Chinese Academy of Medical Sciences
More Information
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Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier: NCT03481998    
Other Study ID Numbers: SHR6390-Ib/II-201
First Posted: March 29, 2018    Key Record Dates
Last Update Posted: June 2, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jiangsu HengRui Medicine Co., Ltd.:
CDK4/6 inhibitor
Breast cancer
Postmenopausal women
 Hormone-receptor positive
HER2 negative
Premenopausal women
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Fulvestrant
Anastrozole
Antineoplastic Agents
Aromatase Inhibitors
 Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists