Efficacy of Everolimus Combined With First-line Endocrine Therapy for HR+/HER2- SNF1-subtype Advanced Breast Cancer

NCT05949541 | Recruiting Phase 2

• 1 other identifier: SCHBCC-N062
• Study Type: interventional
• Target: 265
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, controlled, open-label, phase II study to explore the efficacy and safety of Everolimus in combination with standard first-line endocrine therapy for the HR+/ HER2-SNF1 subtype of advanced breast cancer. The study was used to explore the efficacy of Everolimus in combination with standard endocrine therapy.

Conditions

Breast Cancer; Advanced Breast Cancer

Keywords

luminal breast cancer; advanced breast cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  The interval from randomization until the first occurrence of disease progression (according to RECIST 1.1) or death from any cause, which ever occurs first.

  Approximately 5 years

Secondary Outcomes (4)

• Clinical Benefit Rate (CBR)

  Approximately 5 years

• Objective Response Rate (ORR)

  Approximately 5 years

• Overall Survival (OS)

  Approximately 5 years

• Safety and tolerability

  Approximately 5 years

Study Arms (2)

Arm-A

EXPERIMENTAL

Everolimus + CDK4/6 inhibitor+ Endocrine therapy group: Everolimus, 10mg po. qd; Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle. Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks.

Drug: Everolimus 10 mg; Drug: CDK4/6 Inhibitor SHR6390; Drug: Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors

Arm-B

ACTIVE COMPARATOR

CDK4/6 inhibitor+ Endocrine therapy group: Dalpiciclib 125mg po. qd. for 3 weeks, followed by 1 week off, 4 weeks as a cycle. Aromatase inhibitors (Letrozole/Anastrozole/Exemestane), po. qd. at specific doses (Letrozole 2.5mg/day; Anastrozole 1mg/day, Exemestane 25mg/day); Or Fluvestrant, 500mg im. q28d, (Extra 500mg given after 2 weeks of first dose); Premenopause participants: Goserelin 3.6mg, subcutaneously, once every 4 weeks.

Drug: CDK4/6 Inhibitor SHR6390; Drug: Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors

Interventions

Everolimus 10 mg DRUG

Everolimus is a kind of mTOR inhibitor which has been approved to use in several kinds of cancers, especially in metastatic breast cancer.

Also known as: Afinitor

Arm-A

CDK4/6 Inhibitor SHR6390 DRUG

Dalpiciclib (SHR6390) is a kind of CDK4/6 inhibitor that has demonstrated tolerability and preliminary clinical activity in patients with heavily pretreated hormone receptor-positive, HER2-negative advanced breast cancer.

Also known as: Dalpiciclib

Arm-A; Arm-B

Aromatase inhibitor and Fulvestrant combined with CDK4/6 inhibitors DRUG

Endocrine therapy combined with CDK4/6 inhibitors is the standard first-line therapy for advanced luminal breast cancer. Investigators choose endocrine therapy including Letrozole, Anastrozole, Exemestane, and Fulvestrant. Postmenopausal participants should use Goserelin.

Also known as: Endocrine therapy

Arm-A; Arm-B

Eligibility Criteria

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

You may qualify if:

• Patients need to meet all of the following conditions
• Patients must be ≥18 and ≤ 75 years of age;
• Pathologically confirmed breast cancer is HR+/HER2- breast cancer (IHC ER \>10%, or/and PR\>10%, HER 0 OR +, if HER2++, FISH negative);
• SNF1 subtype definition: SNF1 subtype confirmed by digital pathology of H\&E sections;
• Locally advanced breast cancer (radical local therapy is not possible) or metastatic breast cancer (without using adjuvant CDK4/6 inhibitors in the past, or one year after adjuvant CDK4/6 inhibitor therapy has ended);
• No prior therapy (chemotherapy, targeted therapy, etc.) for advanced or metastatic breast cancer;
• Patients with at least one measurable lesion that has not previously received radiation therapy and can be evaluated repeatedly according to RECIST 1.1;
• The functions of the main organs are basically normal, and the following conditions are met:
• Blood routine examination standards should meet: HB≥90g/L (no blood transfusion within 14 days); ANC≥1.5×109/L; PLT≥75×109/L;
• Biochemical examination shall meet the following standards: TBIL≤1.5×ULN (upper limit of normal value); ALT and AST≤3 x ULN; In case of liver metastasis, ALT and AST≤5×ULN; Serum Cr ≤1.5×ULN, endogenous creatinine clearance \> 50ml/min (Cockcroft-Gault formula);
• ECOG performance status 0 or 1; The expected survival is more than 3 months;
• Fertile female is required to use a medically approved contraceptive during study treatment and for at least 3 months after the last use of the study drug;
• Patients voluntarily join the study, sign the informed consent, have good compliance, and cooperate with follow-up.

You may not qualify if:

• Patients with any of the following conditions were excluded from the study
• Patients with central nervous system metastasis out of control (symptoms need to use glucocorticoids or mannitol).
• A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction within the last 6 months, or ventricular arrhythmia;
• Radiotherapy, chemotherapy, surgery, other targeted therapy and immunotherapy for advanced HR+/HER2- breast cancer within 4 weeks prior to first administration of drugs used in this study.
• Pregnant or lactating patients;
• Other malignancies within the previous 3 years, excluding cured skin basal cell carcinoma and cervical carcinoma in situ;
• Significant comorbid medical conditions, including mental illnesses that the investigator or sponsor believes would adversely affect the patient's participation in the study;
• Allergic physique, or known allergic history of the drug components of this program; Or allergic to other monoclonal antibodies;
• The investigator does not consider the patient suitable for participation in any other circumstances of the study.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Everolimus; dalpiciclib; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• Zhimin Shao, MD,PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhimin Shao, MD, PhD

CONTACT

+86-021-64175590; zhimingshao@yahoo.com

Min He, MD, PhD

CONTACT

+86-021-64175590; min1.he@shca.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of General Surgery of Fudan Shanghai Cancer Center

Study Record Dates

• First Submitted: July 9, 2023
• First Posted: July 18, 2023
• Study Start: July 26, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2028
• Last Updated: February 8, 2024

Record last verified: 2024-02

Locations

CN (1)