SNF Platform Study of HR+/ HER2-advanced Breast Cancer

NCT05594095 | Recruiting Phase 2

• 1 other identifier: BCTOP-L-M05
• Study Type: interventional
• Target: 620
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to establish a prospective, multi-center platform research based on clinical subtypes to explore precision therapy in patients hormone-receptor-positive HER2-negative advanced breast cancer who had previously used CDK4/6 inhibitors.

Conditions

Breast Neoplasm; Breast Cancer; Hormone Receptor Positive Tumor; HER2-negative Breast Cancer; Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)

  Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 3 years)

Secondary Outcomes (5)

• Clinical Benefit Rate (CBR)

  Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 3 years

• Progression Free Survival (PFS)

  Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 3 years)]

• Overall Survival (OS)

  Randomization to death from any cause, through the end of study (approximately 3 years)

• CTCAE scale (V5.0)

  up to One Year during follow-up

• Exploration of translational research markers

  up to One Year during follow-up

Study Arms (26)

SNF1 1A: PIK3CA mutation

EXPERIMENTAL

PIK3CA inhibitors +Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.

Drug: PIK3CA inhibitor; Drug: Aromatase Inhibitors or Fulvestrant; Drug: Goserelin

SNF1 1B: AKT pathway mutation

EXPERIMENTAL

AKT pathway inhibitors +Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.

Drug: AKT inhibitor; Drug: Aromatase Inhibitors or Fulvestrant; Drug: Goserelin

SNF1 1C: without above mutation

EXPERIMENTAL

Everolimus 10mg po qd+Aromatase inhibitors(Letrozole/Anastrozole/Exemestane, po, qd, specific dose (letrozole 2.5mg/ day; Anastrozole 1mg/ day, Exemestane 25mg/ day);Or fulvestrant, 500mg ,im, qm, followed by 500mg im 2 weeks after the first dose; Premenopausal: Goserelin 3.6mg IM every 4 weeks.

Drug: Everolimus; Drug: Aromatase Inhibitors or Fulvestrant; Drug: Goserelin

SNF2 2A

EXPERIMENTAL

Treatment of physician' choice+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib 15mg po qd for 4 weeks as a cycle

Drug: Carrelizumab; Drug: Famitinib; Drug: TPC

SNF3 3A: Stratification of BRCA/PALB2 expression

EXPERIMENTAL

Fluzoparib SHR3162 100mg po qd+Dalpiciclib 125mg po qd for 4 weeks as a cycle

Drug: Fluzoparib; Drug: Dalpiciclib

SNF4 4A: HER2 low

EXPERIMENTAL

SHR-A1811

Drug: SHR-A1811

The control arm

ACTIVE COMPARATOR

Treatment of Physicians' Choice (albumin-paclitaxel, capecitabine, vinorelbine, and irbribulin)

Drug: TPC

SNF3 3B:

EXPERIMENTAL

Fluzoparib SHR3162 100 mg qd+Treatment of physician' choice

Drug: Fluzoparib; Drug: TPC

SNF4 4B:

EXPERIMENTAL

Apatinib 250mg qd+Treatment of physician' choice

Drug: TPC; Drug: Apatinib

SNF1 1D: without above mutation

EXPERIMENTAL

Everolimus 10mg po qd+Treatment of physician' choice

Drug: Everolimus; Drug: TPC

SNF1 1E: HER2 LOW

EXPERIMENTAL

Everolimus 10mg po qd+SHR-A1811

Drug: SHR-A1811; Drug: Everolimus

SNF1 1F: HER2 zero

EXPERIMENTAL

Everolimus 10mg po qd+SHR-A1921

Drug: Everolimus; Drug: SHR-A1921

SNF2 2B: HER2 zero

EXPERIMENTAL

SHR-A1921+Pd-1 mab (Carrelizumab 200mg Q2W)+bevacizumab 7.5mg po ivgt t for 3 weeks as a cycle

Drug: Carrelizumab; Drug: SHR-A1921; Drug: bevacizumab

SNF2 2C:

EXPERIMENTAL

HER3 -ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle

Drug: Carrelizumab; Drug: Famitinib; Drug: SHR-A2009

SNF2 2D:

EXPERIMENTAL

Nectin4-ADC+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle

Drug: Carrelizumab; Drug: Famitinib; Drug: SHR-A2102

SNF2 2E: HER2 low

EXPERIMENTAL

SHR-A1811+Pd-1 mab (Carrelizumab 200mg Q2W)+Famitinib for 3 weeks as a cycle

Drug: Carrelizumab; Drug: Famitinib; Drug: SHR-A1811

SNF3 3C:

EXPERIMENTAL

CDK4i（SHR-6209 PR2D+PARP1i（SHR-1167 PR2D）

Drug: SHR-1167; Drug: SHR-6209

SNF3 3D:

EXPERIMENTAL

PARP1i（SHR-1167 PR2D)+Famitinib 5mg po qd for 4 weeks as a cycle

Drug: Famitinib; Drug: SHR-1167

SNF3 3E: HER2 low

EXPERIMENTAL

PARP1i（SHR-1167 PR2D)+SHR-A1811 for 3 weeks as a cycle

Drug: SHR-A1811; Drug: SHR-1167

SNF3 3F: HER2 zero

EXPERIMENTAL

PARP1i（SHR-1167 PR2D)+SHR-A1921 for 3 weeks as a cycle

Drug: SHR-A1921; Drug: SHR-1167

SNF4 4C

EXPERIMENTAL

Famitinib 20mg po qd

Drug: Famitinib

SNF4 4D

EXPERIMENTAL

Sorafenib 0.4g bid

Drug: Sorafenib

SNF4 4E

EXPERIMENTAL

Apatinib 500mg qd

Drug: Apatinib

SNF4 4F: HER2 low

EXPERIMENTAL

Famitinib+SHR-A1811 for 3 weeks as a cycle

Drug: Famitinib; Drug: SHR-A1811

SNF4 4G

EXPERIMENTAL

Famitinib+HER3-ADC for 3 weeks as a cycle

Drug: Famitinib; Drug: SHR-A2009

SNF4 4H

EXPERIMENTAL

Famitinib+Nectin4-ADC for 3 weeks as a cycle

Drug: Famitinib; Drug: SHR-A2102

Interventions

PIK3CA inhibitor DRUG

PIK3CA inhibitor

SNF1 1A: PIK3CA mutation

AKT inhibitor DRUG

AKT inhibitor

SNF1 1B: AKT pathway mutation

Carrelizumab DRUG

Pd-1 mab

Also known as: SHR1210

SNF2 2A; SNF2 2B: HER2 zero; SNF2 2C:; SNF2 2D:; SNF2 2E: HER2 low

Famitinib DRUG

VEGFR inhibitor

SNF2 2A; SNF2 2C:; SNF2 2D:; SNF2 2E: HER2 low; SNF3 3D:; SNF4 4C; SNF4 4F: HER2 low; SNF4 4G; SNF4 4H

Fluzoparib DRUG

PARP inhibitor

Also known as: SHR3162

SNF3 3A: Stratification of BRCA/PALB2 expression; SNF3 3B:

Dalpiciclib DRUG

CDK4/6 inhibitor

Also known as: SHR6390

SNF3 3A: Stratification of BRCA/PALB2 expression

SHR-A1811 DRUG

HER2 ADC

SNF1 1E: HER2 LOW; SNF2 2E: HER2 low; SNF3 3E: HER2 low; SNF4 4A: HER2 low; SNF4 4F: HER2 low

Everolimus DRUG

mTOR inhibior

SNF1 1C: without above mutation; SNF1 1D: without above mutation; SNF1 1E: HER2 LOW; SNF1 1F: HER2 zero

Aromatase Inhibitors or Fulvestrant DRUG

Letrozole/Anastrozole/Exemestane or Fulvestrant

SNF1 1A: PIK3CA mutation; SNF1 1B: AKT pathway mutation; SNF1 1C: without above mutation

Goserelin DRUG

For premenopause

SNF1 1A: PIK3CA mutation; SNF1 1B: AKT pathway mutation; SNF1 1C: without above mutation

TPC DRUG

Treatment of Physicians' Choice (albumin-paclitaxel, capecitabine, vinorelbine, and irbribulin)

SNF1 1D: without above mutation; SNF2 2A; SNF3 3B:; SNF4 4B:; The control arm

Sorafenib DRUG

RTK Inhibitor

SNF4 4D

Apatinib DRUG

Apatinib 250mg po qd

SNF4 4B:; SNF4 4E

SHR-A1921 DRUG

TROP2 ADC

SNF1 1F: HER2 zero; SNF2 2B: HER2 zero; SNF3 3F: HER2 zero

SHR-A2102 DRUG

NECTIN4 ADC

SNF2 2D:; SNF4 4H

SHR-A2009 DRUG

HER3 ADC

SNF2 2C:; SNF4 4G

SHR-1167 DRUG

PARP1i

SNF3 3C:; SNF3 3D:; SNF3 3E: HER2 low; SNF3 3F: HER2 zero

SHR-6209 DRUG

CDK4i

SNF3 3C:

bevacizumab DRUG

bevacizumab

SNF2 2B: HER2 zero

Eligibility Criteria

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

You may qualify if:

• Female aged ≥18 years;
• HR+/HER2- invasive breast cancer confirmed by histology (specific definition: ER \>10% positive tumor cells by immunohistochemistry is defined as ER positive, PR \>10% positive tumor cells is defined as PR positive, ER and/or PR positive is defined as HR positive; HER2 0-1+ or HER2 + but negative by FISH without amplification was defined as HER2 negative);
• Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer;
• HR+/HER2- advanced breast cancer patients who had previously received CDK4/6 inhibitor therapy;
• At least one measurable lesion according to RECIST 1.1 (conventional CT scan ≥20 mm, spiral CT scan ≥10 mm, measurable lesion has not received radiotherapy);
• The functions of the main organs are basically normal and meet the following conditions:
• I. Blood routine examination criteria shall meet: HB ≥90 g/L (no blood transfusion within 14 days); The ANC acuity 1.5 x 109 / L; PLT acuity 75 x 109 / L; Ii. Biochemical tests should meet the following criteria: TBIL ≤1.5×ULN (upper limit of normal value); ALT and AST ≤3×ULN; If liver metastases were present, ALT and AST≤ 5×ULN; Serum Cr ≤1×ULN, endogenous creatinine clearance \> 50 ml/min (Cockcroft-Gault formula);
• They have not received radiotherapy, molecular targeted therapy, or surgery within 3 weeks before the start of the study, and have recovered from the acute toxicity of previous treatment (if surgery was performed, the wound has healed completely); No peripheral neuropathy or grade I peripheral neurotoxicity;
• ECOG score ≤2, and life expectancy ≥3 months;
• Fertile female subjects were required to use a medically approved contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug;
• Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up.

You may not qualify if:

• Radiotherapy (except for palliative causes), chemotherapy, and immunotherapy were used in the first 3 weeks of treatment, except bisphosphonate (which can be used for bone metastasis);
• Uncontrolled central nervous system metastases (indicating symptomatic or symptomatic treatment with glucocorticoids or mannitol);
• A history of clinically important or uncontrolled heart disease, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmia within the last 6 months;
• Persistent grade 1 or higher adverse reactions caused by previous treatments. The exception to this is hair loss or something the researchers don't think should be ruled out. Such cases should be clearly documented in the investigator's notes;
• Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment;
• Pregnant or lactating patients; Malignancy (except basal cell carcinoma of the skin, which has been cured, and carcinoma in situ of the cervix) in the past 5 years.

Sponsors & Collaborators

• Fudan University: lead
• Peking University Cancer Hospital & Institute: collaborator
• First Hospital of China Medical University: collaborator
• Sun Yat-sen University: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator
• Chongqing University Cancer Hospital: collaborator
• Northern Jiangsu People's Hospital: collaborator
• Fujian Medical University Union Hospital: collaborator
• Ningbo Medical Center Lihuili Hospital: collaborator
• Shanghai First Maternity and Infant Hospital: collaborator
• Shanghai 6th People's Hospital: collaborator
• Affiliated Hospital of Nantong University: collaborator
• Nanchang People's Hospital: collaborator
• Liaoning Cancer Hospital & Institute: collaborator
• The Affiliated Hospital of Nantong University: collaborator
• The First Hospital of Jilin University: collaborator

Study Sites (1)

Breast cancer institute of Fudan University Cancer Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

camrelizumab; famitinib; fluzoparib; dalpiciclib; Everolimus; Aromatase Inhibitors; Fulvestrant; Goserelin; Sorafenib; apatinib; Bevacizumab

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; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Central Study Contacts

Zhimin Shao, M.D

CONTACT

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

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: Professor

Study Record Dates

• First Submitted: October 13, 2022
• First Posted: October 26, 2022
• Study Start: December 30, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 4, 2024

Record last verified: 2023-10

Locations

CN (1)