Clinical trial NCT05594095: SNF Platform Study of HR+/ HER2-advanced Breast Cancer
Official title: Precision Platform Study of HR+/ HER2-advanced Breast Cancer Based on SNF Typing (A Prospective, Open-label, Multi-center, Phase II Platform Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Breast Neoplasm
Breast Cancer
Hormone Receptor Positive Tumor
HER2-negative Breast Cancer
Advanced Breast Cancer
Lead sponsor: Fudan University
Sponsor class: OTHER
Collaborators: name: Peking University Cancer Hospital & Institute
name: First Hospital of China Medical University
name: Sun Yat-sen University
name: First Affiliated Hospital Xi'an Jiaotong University
name: Chongqing University Cancer Hospital
name: Northern Jiangsu People's Hospital
name: Fujian Medical University Union Hospital
name: Ningbo Medical Center Lihuili Hospital
name: Shanghai First Maternity and Infant Hospital
name: Shanghai 6th People's Hospital
name: Affiliated Hospital of Nantong University
name: Nanchang People's Hospital
name: Liaoning Cancer Hospital & Institute
name: The Affiliated Hospital of Nantong University
name: The First Hospital of Jilin University
First posted: 2022-10-26
Enrollment: 620
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 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:
measure: Clinical Benefit Rate (CBR)
timeFrame: 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
measure: Progression Free Survival (PFS)
timeFrame: 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)]
measure: Overall Survival (OS)
timeFrame: Randomization to death from any cause, through the end of study (approximately 3 years)
measure: CTCAE scale (V5.0)
timeFrame: up to One Year during follow-up
measure: Exploration of translational research markers
timeFrame: up to One Year during follow-up
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Breast cancer institute of Fudan University Cancer Hospital
state: Shanghai
Study officials:
References: