Breast Neoplasm, Breast Cancer, Hormone Receptor Positive Tumor, HER2-negative Breast Cancer, Advanced Breast Cancer
Conditions
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.
Detailed description
Participants in this study were hormone-receptor-positive HER2-negative patients with advanced breast cancer who had previously used CDK4/6 inhibitors. Hormone receptor positive HER2 negative was defined as ER positive (IHC ER positive percentage \> 10% or PR positive (IHC PR positive percentage \> 10%) and HER2 negative (IHC-/+; Or IHC++ but FISH/CISH-). The Department of Pathology and the Key Laboratory of Breast Cancer of Fudan University Shanghai Cancer Center conducted digital pathological typing of the biopsy pathology of metastatic lesions of all participants . If the pathology of metastatic lesions could not be obtained, the digital pathological typing was performed according to the pathology of primary lesions. According to the digital pathological types of biopsy tissue and peripheral blood ctDNA, the patients were divided into four precise subtypes: SNF1, SNF2, SNF3, and SNF4. At the same time, the negative control group was randomly set by subtype stratification at 2:1. In different SNF types, patients were divided into 7 subcohorts according to the genetic PANEL results.
Interventions
DRUGPIK3CA inhibitor
PIK3CA inhibitor
DRUGAKT inhibitor
AKT inhibitor
DRUGCarrelizumab
Pd-1 mab
DRUGFamitinib
VEGFR inhibitor
DRUGFluzoparib
PARP inhibitor
DRUGDalpiciclib
CDK4/6 inhibitor
DRUGSHR-A1811
HER2 ADC
DRUGEverolimus
mTOR inhibior
DRUGAromatase Inhibitors or Fulvestrant
Letrozole/Anastrozole/Exemestane or Fulvestrant
DRUGGoserelin
For premenopause
DRUGTPC
Treatment of Physicians' Choice (albumin-paclitaxel, capecitabine, vinorelbine, and irbribulin)
DRUGSorafenib
RTK Inhibitor
DRUGApatinib
Apatinib 250mg po qd
DRUGSHR-A1921
TROP2 ADC
DRUGSHR-A2102
NECTIN4 ADC
DRUGSHR-A2009
HER3 ADC
DRUGSHR-1167
PARP1i
DRUGSHR-6209
CDK4i
DRUGbevacizumab
bevacizumab
Sponsors
Peking University Cancer Hospital & Institute
First Hospital of China Medical University
Sun Yat-sen University
First Affiliated Hospital Xi'an Jiaotong University
Chongqing University Cancer Hospital
Northern Jiangsu People's Hospital
Fujian Medical University Union Hospital
Ningbo Medical Center Lihuili Hospital
Shanghai First Maternity and Infant Hospital
Shanghai 6th People's Hospital
Affiliated Hospital of Nantong University
Nanchang People's Hospital
Liaoning Cancer Hospital & Institute
The Affiliated Hospital of Nantong University
The First Hospital of Jilin University
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female aged ≥18 years; 2. 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); 3. Locally advanced breast cancer (unable to undergo radical local treatment) or recurrent metastatic breast cancer; 4. HR+/HER2- advanced breast cancer patients who had previously received CDK4/6 inhibitor therapy; 5. 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); 6. 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); 7. 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; 8. ECOG score ≤2, and life expectancy ≥3 months; 9. 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; 10. Subjects volunteered to join the study, signed informed consent, had good compliance, and cooperated with follow-up.
Exclusion criteria
1. 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); 2. Uncontrolled central nervous system metastases (indicating symptomatic or symptomatic treatment with glucocorticoids or mannitol); 3. 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; 4. 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; 5. Underwent major surgery (except minor outpatient procedures, such as placement of vascular access) within 3 weeks of the first course of trial treatment; 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 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) | The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | the percentage of subjects with CR+PR+SD and last more than 24 weeks in all of the subjects |
| 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)] | time to progressive disease (according to RECIST1.1) |
| Overall Survival (OS) | Randomization to death from any cause, through the end of study (approximately 3 years) | time to death due to any cause |
| CTCAE scale (V5.0) | up to One Year during follow-up | To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V5.0) |
| Exploration of translational research markers | up to One Year during follow-up | The collected subjects' tumor tissues, paracancerous tissues, blood, and fecal samples will be used for discovering exploratory biomarkers. The relationships between discovered biomarkers and subjects' disease status and treatment responses will also be investigated. |
Countries
China
Contacts
Primary ContactZhimin Shao, M.D
Outcome results
None listed