A Phase II, Open-label, Single Arm, Investigator-initiated Trail of An Anti-PD-1 Inhibitor SHR-1210 in Combination With Apatinib in the Perioperative Treatment of Hepatocellular Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Apatinib Combined With SHR-1210 Injection
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- The First Affiliated Hospital with Nanjing Medical University
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Major pathologic response
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a Phase II , Open-label , Investigator-initiated Trail of SHR-1210 (an Anti-PD-1 Inhibitor) in Combination With Apatinib in Patients With Hepatocellular Carcinoma(HCC).This study aims to evaluate the safety and efficacy of SHR-1210 combination with Apatinib as a preoperative treatment of HCC.
Detailed Description
This is an Open, Single Arm, Exploratory and Phase II Clinical Trial of Apatinib Combined With SHR-1210 (an Anti-PD-1 Inhibitor) in Patients With Hepatocellular Carcinoma(HCC) as Perioperative Treatment. we conduct this study in order to observe and evaluate the efficacy and safety of Apatinib combined with SHR-1210 (an Anti-PD-1 Inhibitor) in treatment of patients with HCC. Primary Efficacy Endpoint: Major pathologic response (MPR), Secondary Efficacy Endpoints: Pathological complete response Rate (pCR), Objective Response(ORR) (According to RECIST Version 1.1), Recurrence-free survival(RFS) and Overall survival rate of 6 months (OS %-6 m). Safety and tolerance will be evaluated by incidence, severity and outcomes of AEs and categorized by severity in accordance with the NCI CTC AE Version 4.0.3.
Investigators
Eligibility Criteria
Inclusion Criteria
- •The patient volunteered to participate in the study and signed an informed consent form
- •≥18 years of age，Male or female
- •Subjects are diagnosed with histologically or cytologically confirmed HCC
- •Subjects haven't received any systemic treatment for HCC before admission.
- •Subjects enrolled must have measurable lesion(s) according to the RECIST 1.1 standard
- •ECOG performance status of 0 or 1
- •Life expectancy ≥ 12 weeks
- •Subjects are diagnosed with resectable stage IIB, stage IIIA HCC cancer.
- •The main organ's function is normal and it should meet the following criteria(Excludes use of any blood components and cell growth factors during the screening period)
- •Absolute neutrophil count≥1.5×109 /L
Exclusion Criteria
- •Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma; other active malignant tumor except HCC within 5 years or simultaneously
- •Be ready for or previously received organ or allogenic bone marrow transplantation
- •Moderate-to-severe ascites with clinical symptoms
- •History of gastrointestinal hemorrhage within 6 months prior to the start of study treatment or clear tendency of gastrointestinal hemorrhage.
- •Abdominal fistula, gastrointestinal perforation or intraperitoneal abscess within 6 months prior to the start of study treatment.
- •Known genetic or acquired hemorrhage or thrombotic tendency.
- •The patient is currently using or has recently used (within 10 days before the start of study treatment) aspirin (\> 325mg / day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel and cilostazol.
- •Thrombosis or thromboembolic event within 6 months prior to the start of study treatment.
- •Cardiac clinical symptom or disease that is not well controlled.
- •Subjects have uncontrollable hypertension (systolic pressure ≥ 140 mmHg or diastolic pressure ≥ 90 mmHg), despite patients have taken the best drug treatment ；Subjects have had a hypertensive crisis or hypertensive encephalopathy
Arms & Interventions
Apatinib Combined With SHR-1210 Injection
SHR-1210 Injection: 3 cycles of neoadjuvant therapy before surgery, two weeks is a treatment cycle; Apatinib : D1-D21 : 250 mg, orally, qd; Before surgery, the patient's surgical pathology samples still need to be collected. D46 : Patients were preoperatively evaluated. Operable patients were scheduled for hepatectomy with/without microwave ablation; After 4 to 8 weeks after liver resection, a postoperative adjuvant program is performed. The cycle of a three-week plan will be performed with a total of 8 cycles with the treatment of Apatinib combination with SHR-1210 Injection.
Intervention: Apatinib Combined With SHR-1210 Injection
Outcomes
Primary Outcomes
Major pathologic response
Time Frame: 6 months
It is defined as residual tumors less than 10% after neo-adjuvant therapy
Secondary Outcomes
- Safety as measured by the rate of AEs(through study completion, an average of 1 year)
- Pathological complete response(6 months)
- Overall survival rate (6 m or 12 m)(through study completion; the rate of OS for 6 months and 12 months)
- Objective Response(ORR)(Before surgery；)
- Recurrence free survival(RFS)(through study completion, an average of 1 year)
- Recurrence free survival rates of 6 months and 12 months(12 months)