Breast Cancer
Conditions
Brief summary
This is a Phase II, Open-labeled, Randomised, Parallel, Non-comparative, Two-arms, Investigator-initiated Clinical Trial of SHR-1210 (Anti-PD-1 Antibody) in Combination With Apatinib (VEGFR2 inhibitor) in Subjects with Advanced Triple Negative Breast Cancer. Subjects with advanced Triple Negative Breast Cancer will be recruited. Patients will be randomised to two treatment arms of this study. One arm is SHR-1210 combination with apatinib daily dosing, and the other arm is SHR-1210 combination with apatinib intermittent dosing; each arm will enrolle10-29 subjects (Simons two stage design). This study aims to evaluate the efficacy and safety of SHR-1210 combination with apatinib in the treatment of advanced TNBC.
Interventions
DRUGSHR-1210
SHR-1210 200mg (3mg/kg for patient whose weight is below 50kg) will be administered as an intravenous infusion over 30 minutes every two weeks until unacceptable toxic effects or disease progression or other termination criteria appeared.
DRUGApatinib
Apatinib 250mg will be taked daily/intermittent dosing until unacceptable toxic effects or disease progression or other termination criteria appeared.
Sponsors
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* The patients signed the written informed consent * Women aged 18-70. * The pathologic diagnosis of recurrent metastatic triple negative breast cancer ［ER-negative(IHC\<1%), PR-negative(IHC\<1%), HER2-negative（IHC-/+ or IHC++ and FISH/CISH-）］. * At least one measuring lesion that conforms to RECIST v1.1 standard. * The number of chemotherapy lines in the metastatic phase was \<3 line. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1. * Have a life expectancy of at least 12 weeks. * Female Subjects of childbearing potential must have a negative serum pregnancy test within 72 hours before the first dose and must be willing to use very efficient barrier methods of contraception for the course of the study through 3 months after the last dose of study treatment. * The patients can swallow pills. * The results of patients' blood tests are as follows: • Hb≥90g/L; • Plt≥90E+9/L; • Neutrophils≥1.5E+9/L; • ALT and AST ≤ triple of normal upper limit; • TBIL ≤ 1.5 times of normal upper limit; • Creatinine ≤ 1.5 times of normal upper limit.
Exclusion criteria
* The subjects had any history of autoimmune disease or any use of systemic glucocorticoid or immunosuppressive medications. * Subjects with severe allergic reactions to other monoclonal antibodies. * The subjects had a central nervous system metastases with clinical symptoms. * History of hypertension and antihypertensive medications are not well controlled. * A heart condition or disease that is not well controlled. * Subjects had active infections or recent treatment with a systemic immunostimulatory agent (received within the previous 4 weeks). * Other clinical trials of drugs were used in the first four weeks of the first medication. * Subjects with treatment history of anti-angiogenesis drugs or check-point inhibitors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | from the first drug administration up to the first occurrence of progression or death(up to 24 months) | Overall Response Rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | from the first drug administration to within 90 days for the last SHR-1210 dose | adverse events/serious adverse events |
| DCR | from the first drug administration up to the first occurrence of progression or death(up to 24 months) | Disease Control Rate |
| PFS | from the first drug administration up to the first occurrence of progression or death (up to about 5 years) | Progression-Free-Survival |
| DoR | from the first drug administration up to the first occurrence of progression or death(up to 24 months) | Duration of response |
| CBR | from the first drug administration up to the first occurrence of progression or death(up to 24 months) | Clinical benefit rate |
| TTR | from the first drug administration up to one year | Time to response |
| Frequencies Of Biomarkers | pre-dose, and up to two years | Biomarkers (PD-L1, PD-1, VEGF-A, eg) in tumor tissue and peripheral blood |
| One year-OS | 12 months after the first drug administration | One year-Overall survival |
Countries
China
Outcome results
None listed