Breast Cancer, Metastatic Cancer
Conditions
Keywords
first-line therapy
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.
Interventions
DRUGSHR7390
MEK1/2 inhibitor
DRUGFamitinib
Multi-target tyrosine kinase inhibitor
DRUGSHR3162
PARP inhibitor
DRUGPyrotinib
HER1 / HER2 receptor tyrosine kinase inhibitor
DRUGCapecitabine
In Arm III, if the patient had not previously used capecitabine,she would receive pyrotinib and capecitabine, if the patients have previously used capecitabine, she would only used pyrotinib as a single agent.
DRUGSHR1210
PD-1 antibody
DRUGEverolimus
mTOR inhibitor
DRUGNab paclitaxel
Albumin bound paclitaxel
DRUGSHR2554
EZH2 inhibitor
DRUGSHR3680
AR inhibitor
DRUGSHR6390
CDK4/6 inhibitor
DRUGSHR1701
anti-PD-L1/TGF-βRII bifunctional fusion protein
DRUGSERD
Fulvestrant
DRUGAI
aromatase inhibitor
DRUGVEGFi
Bevacizumab
Sponsors
Fudan University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 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) | The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CBR | 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) | the percentage of subjects with CR+PR+SD and last more than 24 weeks in all of the evaluable subjects |
| PFS | 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) | time to progressive disease (according to RECIST1.1) |
| OS | Randomization to death from any cause, through the end of study (approximately 5 years) | time to death due to any cause |
Countries
China
Contacts
Primary ContactZhi-Ming Shao
Backup ContactZhong-Hua Wang
Outcome results
None listed