NCT02942329
Unknown
Phase 1
Exploratory Clinical Study of the Combination of Apatinib and SHR-1210 in Treating Advanced Hepatocellular Carcinoma or Gastric Cancer
The Affiliated Hospital of the Chinese Academy of Military Medical Sciences1 site in 1 country60 target enrollmentStarted: October 2016Last updated:
Overview
- Phase
- Phase 1
- Sponsor
- The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Overall survival rate
Overview
Brief Summary
The purpose of this study is to observe and preliminary explore the efficacy and safety of combination of Apatinib and SHR-1210 regimen in treating advanced hepatocellular carcinoma or gastric cancer.
Apatinib is a small-molecule vascular endothelial growth factors receptor (VEGFR) tyrosine kinase inhibitor, similar to vatalanib (PTK787), but with a binding affinity 10 times that of vatalanib or sorafenib.
SHR-1210 is a humanized anti-PD-1 monoclonal antibody.
Detailed Description
Patients will received apatinib orally every day and SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks. The efficacy and safety will be observed.
The dose escalation phase has completed for apatinib from 125mg, 250mg to 500mg. The dose of 250mg showed best tolerance and efficacy especially in hepatocellular carcinoma. Thus, for hepatocellular carcinoma patients, apatinib 250mg orally every day was chosed for the dose extension phase. In gastric cancer, the dose of 250mg also showed good tolerance but mild efficacy. Thus, for gastric cancer patients, the dose of 375mg daily for apatinib would be explored and then the investigators will decide the best dosage for these patients.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Inclusion criteria
- •Aged 18-70 years old, both genders.
- •To be confirmed to meet the clinical diagnosis standard, histologically or cytologically confirmed with hepatocellular carcinoma or gastric cancer. Patients must be diagnosed with advanced disease(not eligible for surgical and/or locoregional therapies, or metastatic disease), disease progressed or refractory to standard therapies(had been intolerant to standard therapies, or had refused standard therapy), or lack of other effective treatment methods.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or
- •Life expectancy of at least 3 months.
- •Patients must have at least 1 lesion that is measurable using RECIST v1.1 criteria.
- •For patients with advanced hepatocellular carcinoma, liver function status Child-Pugh Class A or B (score\<=7).
- •Patients must have adequate organ function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment)as determined by: Hemoglobin ≥ 9 g/dL; Absolute neutrophil count (ANC) ≥1.5×109/L; Platelet count ≥ 75×109/L (for patients with advanced hepatocellular carcinoma), Platelet count ≥ 100×109/L (for patients with advanced gastric cancer); serum albumin ≥2.8 g/dL; serum total bilirubin (TBIL)≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×upper limit of normal(ULN), for subjects with liver metastases, ALT and AST≤5×ULN; Calculated creatinine clearance (CrCl) \> 50 mL/min (Cockcroft-Gault formula will be used to calculate CrCl).
- •Females of childbearing potential (FOCBP), who are not surgically sterile or postmenopausal, must conduct pregnancy test (serum or urine) within 7 days before enrollment, and must not be pregnant or breast-feeding women. If the result is negative, she must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs. And non-sterilized males who are sexually active must agree to use adequate contraception during the experiment and 3 months after the last administration of the test drugs.
- •Patients join the study voluntarily, sign a consent form, have good compliance, and comply with follow-up.
Exclusion Criteria
- •Patients must not have had prior treatment with SHR-1210 or any other PD-L1 or PD-1 antagonists, and must not have had be enrolled in the phase III Study of Apatinib After Systemic Therapy in Patients With Hepatocellular Carcinoma.
- •Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
- •Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration. Note: corticosteroids used for the purpose of IV contrast allergy prophylaxis are allowed.
- •Known history of hypersensitivity to any components of the SHR-1210 formulation, or other antibody formulation.
- •Active central nervous system (CNS) metastases with clinical symptoms (including cerebral edema, steroid requirement, or progressive disease). Subjects with brain or meningeal metastases that were previously treated must be clinically stable (magnetic resonance imaging \[MRI\] at least 4 weeks apart do not show evidence of new or enlarging metastases) and have discontinued immunosuppressive doses of systemic steroids (\> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration.
- •Patients with other malignant tumor (except cured skin basal cell carcinoma and cervical carcinoma).
- •Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class \> 2), ventricular arrhythmia which need medical intervention, left ventricular ejection fraction(LVEF) \< 50%.
- •Hypertension and unable to be controlled within normal level following treatment of anti-hypertension agents(within 3 months): systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg.
- •Coagulation abnormalities (PT\>16s、APTT\>43s、TT\>21s、Fbg\<2g/L), with bleeding tendency or are receiving thrombolytic or anticoagulant therapy.
- •Prior systemic chemotherapy, radiotherapy, immunotherapy, hormone therapy, surgery or target therapy within 4 weeks (Or 5 half-life of the drug, calculate the longer ) before the study drug administration, or any unresolved AEs \> Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 (with the exception of any stable chronic toxicities not expected to resolve).
Arms & Interventions
apatinib and SHR-1210
Experimental
Every patients will received apatinib orally every day and SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks until disease progression or intolerance of side effects.
Intervention: apatinib (Drug)
apatinib and SHR-1210
Experimental
Every patients will received apatinib orally every day and SHR-1210 200mg (3mg/kg for underweight patients) iv every 2 weeks until disease progression or intolerance of side effects.
Intervention: SHR-1210 (Drug)
Outcomes
Primary Outcomes
Overall survival rate
Time Frame: Up to approximately 12 months
6 months and 12 months
Secondary Outcomes
- Duration of response(Up to approximately 12 months)
- Tumor response rate(Up to approximately 12 months)
- Disease control rate(Up to approximately 12 months)
- Safety as measured by the rate of AEs, deaths and laboratory abnormalities (e.g. Grade 3 or higher per CTCAE v4 )(From the first assignment of informed consent form up to 90 days after the last dose)
Investigators
Study Sites (1)
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