Clinical trial NCT04355858: Molecularly Targeted Umbrella Study in Luminal Advanced Breast Cancer
Official title: Precision Treatment of Luminal Advanced Breast Cancer Based on Molecular Subtyping
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Metastatic Cancer
Keywords: first-line therapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2020-04-21
Enrollment: 319
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a prospective, single-center, open-label, umbrella-shaped phase II clinical study for patients with HR+/HER2- endocrine-resistant advanced breast cancer.

Detailed description: Seven precision treatment cohorts, which targeting NF1 mutation, gBRCA mutation,HER2 mutation, FDGFRb mutation PAM pathway mutations, CD8 and AR, as long as an epigenetic therapy cohort and a combined immunization cohort were initially set up based on gene expression profiles and molecular pathways. The main purpose is to screen valuable treatment cohorts and prepare for subsequent randomized controlled phase III clinical studies with larger sample size.

Eligibility criteria: Inclusion Criteria:

* Females ≥18 years old;
* Histologically confirmed HR + / HER2- invasive breast cancer (specific definition: immunohistochemical detection of ER\> 10% tumor cell positive is defined as ER positive, PR\> 10% tumor cell positive is defined as PR positive, ER and / or PR Positive is defined as HR positive; HER2 0-1 + or HER2 is ++ but negative followed by FISH detection, no amplification, defined as HER2 negative);
* Locally advanced breast cancer (incapable of radical local treatment) or recurrent metastatic breast cancer;
* Patients with HR+/HER2- advanced breast cancer who were previously treated with CDK4 / 6 inhibitor except for Arm 5E-5F;
* Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
* Has adequate bone marrow function: absolute neutrophil count \> 1.5x10ˆ9 /L; platelet count \> 75x10ˆ9 /L, hemoglobin \> 9g/dL;
* Has adequate liver function: alanine aminotransferase (ALT) ≤1.5×upper limit of normal (ULN), aspartate aminotransferase (AST) ≤3×ULN, alkaline phosphatase (AKP) ≤3×ULN, total bilirubin (TBIL) ≤ 1.5×ULN.
* Has adequate kidney function: serum creatinine ≤1×ULN.Endogenous creatinine clearance\> 50 ml / min (Cockcroft-Gault formula);
* Did not receive radiation, molecular targeted therapy or surgery within 3 weeks before the study began, and has recovered from the acute toxicity of previous treatment (if surgery, the wound has completely healed); no peripheral neuropathy or first degree peripheral neurotoxicity ;
* ECOG score ≤ 2 and life expectancy ≥ 3 months;
* Participants voluntarily joined the study, has signed informed consent before any trial related activities are conducted, has good compliance and has agreed to follow-up.

Exclusion Criteria:

* Treatment with chemotherapy, radiotherapy, immunotherapy or surgery (outpatient clinic surgery excluded)within3 weeks prior to initiation of study treatment(bisphosphonates can be used for bone metastasis);
* Symptomatic, untreated, or actively progressing CNS metastases(glucocorticoids or mannitol needed to control symptoms);
* Significant cardiovascular disease(including congestive heart failure, angina pectoris, myocardial infarction or ventricular arrhythmia in the last 6 months);
* Grade ≥ 1 adverse reactions that are ongoing due to previous treatment. Exceptions to this are hair loss or the investigator's opinion should not be ruled out. Such cases should be clearly documented in the investigator's notes;
* Is pregnant or breast feeding;
* Malignant tumors in the past five years (except cured skin basal cell carcinoma and cervical carcinoma in situ).

Primary outcomes:
measure: 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 5 years)
Secondary outcomes:
measure: 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 5 years)
measure: 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 5 years)
measure: OS
timeFrame: Randomization to death from any cause, through the end of study (approximately 5 years)
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Cancer Hospital Affiliated to Fudan University
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhi-Ming Shao
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chen MK. Efficacy of PARP inhibition combined with EZH2 inhibition depends on BRCA mutation status and microenvironment in breast cancer. FEBS J. 2021 May;288(9):2884-2887. doi: 10.1111/febs.15730. Epub 2021 Feb 11.