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

NCT03481998 | Completed Phase 1

• 1 other identifier: SHR6390-Ib/II-201
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 4

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.

Conditions

Advanced Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With adverse events (AEs) and serious adverse events (SAEs) at Phase 1

  Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03. Up to 24 months.

  Up to 4 weeks

Secondary Outcomes (8)

• Area under the plasma concentration versus time curve (AUC) of SHR6390

  Up to 4 weeks

• Peak Plasma Concentration (Cmax) of SHR6390

  Up to 4 weeks

• The time of SHR6390 to reach the maximum concentration (Tmax)

  Up to 4 weeks

• Half-time (t1/2) of SHR6390

  Up to 4 weeks

• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Up to approximately 24 months.

Study Arms (5)

Cohort 1 (Part 1)

EXPERIMENTAL

Participants receive SHR6390 (at protocol defined dose levels) in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).

Drug: SHR6390; Drug: Letrozole or anastrozole or Fulvestrant

Cohort 2 (Part 1)

EXPERIMENTAL

SHR6390 (TBD), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).

Drug: SHR6390; Drug: Letrozole or anastrozole or Fulvestrant

SHR6390 + Letrozole or anastrozole (Part 2)

EXPERIMENTAL

SHR6390 (RP2D, recommended Phase 2 dose), in combination with letrozole 2.5 mg or anastrozole 1mg, orally once daily (continuously).

Drug: SHR6390; Drug: Letrozole or anastrozole or Fulvestrant

SHR6390 + Fulvestrant Cohort 3 (Part 1)

EXPERIMENTAL

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; Drug: Letrozole or anastrozole or Fulvestrant

SHR6390 + Fulvestrant Cohort 4 (Part 1)

EXPERIMENTAL

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; Drug: Letrozole or anastrozole or Fulvestrant

Interventions

SHR6390 DRUG

SHR6390 150 mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

Cohort 1 (Part 1); Cohort 2 (Part 1); SHR6390 + Fulvestrant Cohort 3 (Part 1); SHR6390 + Fulvestrant Cohort 4 (Part 1); SHR6390 + Letrozole or anastrozole (Part 2)

Letrozole or anastrozole or Fulvestrant DRUG

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

Cohort 1 (Part 1); Cohort 2 (Part 1); SHR6390 + Fulvestrant Cohort 3 (Part 1); SHR6390 + Fulvestrant Cohort 4 (Part 1); SHR6390 + Letrozole or anastrozole (Part 2)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has the pathologically-confirmed diagnosis of locally recurrent or metastatic, hormone-receptor positive, HER2 negative Breast Cancer.
• Age: 18 - 75 years old, postmenopausal women.prepostmenopausal women, but should receive Ovary castration.
• 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:
• 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.
• One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy.
• \. 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

You may not qualify if:

• Confirmed diagnosis of HER2 positive disease
• 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.
• Patients who received prior treatment with any CDK4/6 inhibitor, everolimus,fulvestant.
• 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.

Sponsors & Collaborators

• Jiangsu HengRui Medicine Co., Ltd.: lead

Study Sites (4)

Ha'erbin Tumor Hospital

Harbin, Heilongjiang, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Sir Run Run Shaw Hospital of Zhejiang University

Hangzhou, Zhejiang, China

Location

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, China

Location

Related Publications (1)

• Zhang Q, Zhang P, Yan M, Yan X, Wang X, Gu Y, Qu X, Li S, Xu G, Zhu X, Xu B. Dalpiciclib in combination with letrozole/anastrozole or fulvestrant in HR-positive and HER2-negative advanced breast cancer: results from a phase Ib study. Ther Adv Med Oncol. 2024 Sep 2;16:17588359241273026. doi: 10.1177/17588359241273026. eCollection 2024.

  PMID: 39229468 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Anastrozole; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Binhe Xu, MD

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 29, 2018
• Study Start: March 22, 2018
• Primary Completion: July 30, 2022
• Study Completion: July 30, 2022
• Last Updated: November 21, 2023

Record last verified: 2023-11

Locations

CN (4)