Clinical trial NCT05904964: Disitamab Vedotin (RC48) in Hormone Receptor Positive, HER2-low Metastatic Breast Cancer (the Rosy Trial)
Official title: Disitamab Vedotin or Endocrine Therapy for Patients With Metastatic Breast Cancer With Hormone Receptor-positive and HER2-low-expression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: HR Positive/HER2 Low Expression Metastatic Breast Cancer
Keywords: HR positive
HRE2 low expression
metastatic breast cancer
ADC
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2023-06-15
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients were randomly assigned to disitamab vedotin or endocrine therapy
Primary purpose: TREATMENT

Brief summary: Hormone receptor positive, HER2-low expression metastatic breast cancer is the main type of breast cancer, accounting for about 50% - 60%. However, this type of patients lack ideal therapeutic drugs after the failure of first-line standard endocrine therapy, and the median overall survival time is only 30 months. Therefore, finding more efficient and safe therapeutic drugs for these patients has become a big clinical challenge at present. Disitamab Vedotin (DV), as a new class I Antibody-Drug Conjugates drug, can achieve high efficiency and precise tumor killing effect with low toxicity. According to previous study with same sample size, DV also showed good efficacy in metastatic breast cancer with Hormone receptor positive and HER2- low expression as a posterior line treatment.Therefore, we intend to explore the efficacy and safety of DV in the treatment of HER2-low expressioin /Hormone receptor positive metastatic breast cancer patients with endocrine resistance through a scientifically designed, randomized, phase III clinical study.


Eligibility criteria: Inclusion Criteria:

1. Adult female patients (aged 18-70 years, including 18 and 70 years) with metastatic breast cancer confirmed by pathology or imaging are not suitable for surgical resection or radiotherapy for the purpose of cure;
2. Pathological examination confirmed that ER and / or PR were positive, and HER-2 was low expression (ER expression: immunohistochemical staining of tumor cells ≥ 10%; PR expression: immunohistochemical staining of tumor cells ≥ 10%; HER2-low: immunohistochemical staining of 2 + and FISH is not expanded, IHC 1 +);
3. Patients who have received endocrine therapy ;
4. According to the efficacy evaluation criteria for solid tumors (RECIST) version 1.1, there is at least one evaluable target lesion or only osteolytic bone metastasis;
5. Patients with stable brain metastasis or asymptomatic brain metastasis;
6. ECOG physical condition score ≤ 2 points, and the estimated survival time is not less than 3 months;
7. Prior treatment-related toxicity must be relieved to ≤ 1 degree (according to NCI CTCAE 5.0) before enrollment (except for hair loss or other toxicity that is considered as no risk to the safety of patients according to the judgment of the researcher);
8. Adequate bone marrow functional reserve: a. WBC ≥ 3.0 × 10 \^ 9 ／ L, b. Neutrophil count (ANC) ≥ 1.5 × 10 \^ 9 ／ L, c. Platelet count (PLT) ≥ 70 × 10\^9／L;
9. Liver, kidney and heart function tests were basically normal within one week before enrollment (based on the normal values of laboratories in each research center): A. total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN), B. alanine aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5xuln), C. serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 60 ml / min; d. left ventricular ejection fraction (LVEF) ≥ 55%, e. QTcF(Fridericia correction) ≤ 470 ms;
10. Patients understand the research process, voluntarily participate in the research, and sign the informed consent form.

Exclusion Criteria:

1. Patients who had received chemotherapy, radiotherapy, immunotherapy, and endocrine therapy for breast cancer within 2 weeks before enrollment.;
2. Patients who had performed major surgery within 2 weeks before enrollment.
3. Severe heart disease or discomfort within 12 months, including, but not limited to, the following: unstable angina pectoris, myocardial infarction, cerebral hemorrhage and cerebral infarction (except for silent lacunar cerebral infarction without treatment);
4. Have active autoimmune diseases (such as corticosteroids or immunosuppressive drugs) requiring systemic treatment in the past 2 years, excluding those with adrenal insufficiency requiring corticosteroid replacement therapy;
5. Have a clear history of neurological or mental disorders, including epilepsy or dementia;
6. According to the judgment of the researchers, there are some accompanying diseases that seriously endanger the safety of patients or affect patients to complete the study.
7. Those who have been known to have allergic history to Disitamab Vedotin or similar drugs;
8. According to the estimation of the investigator , the patient's compliance with the clinical study is insufficient or the researcher believes that there are other factors that are not suitable for the study.

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: 24 months
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 36 months
measure: Objective response rate (ORR)
timeFrame: 12 months
measure: Disease Control Rate (DCR)
timeFrame: 12 months
measure: Clinical Benefit Rate (CBR)
timeFrame: 12 months
measure: Quality of life assessed by EORTC-C30
timeFrame: 12 months
measure: Psychological condition assessed by GAD-7
timeFrame: 12 months
measure: Pittsburgh Sleep Scale
timeFrame: 12 months
measure: Incidence of adverse events(AE)
timeFrame: from the date of enrollment to one year
measure: Biomarkers and treatment sensitivity analysis
timeFrame: 12 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
city: Shantou
country: China
facility: The Second Affiliated Hospital， Shantou University Medical College
state: Guangdong
city: Qionghai
country: China
facility: Hainan Qionghai People's Hospital
state: Hainan
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Ying Wang
role: PRINCIPAL_INVESTIGATOR
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