Clinical trial NCT03394287: A Trial of SHR-1210 (an Anti-PD-1 Antibody) in Combination With Apatinib in Patients With Advanced TNBC
Official title: A Phase II, Open-labeled, Randomised, Non-comparative, Two-arms Investigator-initiated Clinical Trial of SHR-1210 (Anti-PD-1 Antibody) in Combination With Apatinib in Subjects With Advanced Triple Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2018-01-09
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: ORR
timeFrame: from the first drug administration up to the first occurrence of progression or death(up to 24 months)
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events
timeFrame: from the first drug administration to within 90 days for the last SHR-1210 dose
measure: DCR
timeFrame: from the first drug administration up to the first occurrence of progression or death(up to 24 months)
measure: DoR
timeFrame: from the first drug administration up to the first occurrence of progression or death(up to 24 months)
measure: PFS
timeFrame: from the first drug administration up to the first occurrence of progression or death (up to about 5 years)
measure: One year-OS
timeFrame: 12 months after the first drug administration
measure: CBR
timeFrame: from the first drug administration up to the first occurrence of progression or death(up to 24 months)
measure: TTR
timeFrame: from the first drug administration up to one year
measure: Frequencies Of Biomarkers
timeFrame: pre-dose, and up to two years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Erwei Song
role: PRINCIPAL_INVESTIGATOR
References:
citation: Liu J, Liu Q, Li Y, Li Q, Su F, Yao H, Su S, Wang Q, Jin L, Wang Y, Lau WY, Jiang Z, Song E. Efficacy and safety of camrelizumab combined with apatinib in advanced triple-negative breast cancer: an open-label phase II trial. J Immunother Cancer. 2020 May;8(1):e000696. doi: 10.1136/jitc-2020-000696.