Combination Camrelizumab (SHR-1210) and Apatinib for Downstaging/Bridging of HCC Before Liver Transplant

A Single Group, Open Label, Multi-center Clinical Study of Combination Camrelizumab (SHR-1210) and Apatinib for Downstaging/Bridging of Hepatocellular Cancer Before Liver Transplant

To assess the primary effects and safety of camrelizumab (SHR-1210) plus apatinib for downstaging/bridging of HCC before liver transplantation.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma; Liver Transplant
• Intervention / Treatment: Drug: Camrelizumab plus apatinib

Detailed Description

HCC patients waiting for liver transplantation will be screened and enrolled according to the inclusion criteria. After screening and enrollment, patients will be administrated camrelizumab 200mg q2w iv and apatinib 250mg qd po regimen every 4 weeks as a cycle. Each patient will receive camrelizumab treatment for at least 2 cycles and discontinue camrelizumab 5 weeks before liver transplantation. Apatinib will be discontinued 1 week before liver transplantation. Once the tumor progression was detected, the program will be terminated and the appropriate optimal treatment will be given. The objective remission rate (ORR), recurrence-free survival (RFS), overall survival (OS), time to progress (TTP) and any adverse effect during the study will be evaluated in order to assess the primary effects and safety of camrelizumab (SHR-1210) plus apatinib for downstaging/bridging of HCC before liver transplantation.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The First Affiliated Hospital of Medical School of Zhejiang University
      • Contact: Jianguo Wang, PhD; Phone Number: (+86)15967123327

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18-75 years
• Pathology: hepatocellular carcinoma
• Exceed Hangzhou Criteria (Type A: diameter of tumor ≤ 8 cm or diameter of tumor and AFP ≤ 100 ng/mL; Type B: diameter of tumor >8 cm, but 100 ng/mL < AFP <400 ng/mL)
• No interventional therapy (TACE, RFA or I131) within 2 month
• Expected survival for more than 3 months
• Child-pugh grade A or grade B (≤ 7 points)
• Absolute neutrophil count ≥ 1.5×10^9 /L, Hb ≥ 9 g/L, PLT ≥ 100×10^9 /L; TSH ≤ ULN; total bilirubin ≤ 1.5 ULN, albumin ≥ 28 g/L, AST, ALT ≤ 3 ULN; serum creatinine ≤ 1.5 ULN
• ECOG: 0-2
• Patients participate in the study voluntarily and sign informed consent

Exclusion Criteria:

• Regional lymph node metastases or extrahepatic metastases
• Allergic to Camrelizumab or Apatinib
• Patients who have had or are currently complicated with other malignant tumors
• Active hepatitis (hepatitis B: HBsAg positive or HBV- DNA≥10⁴copies/ml; hepatitis C: HCV antibodies and HCV-RNA positive)
• Activ pulmonary tuberculosis or pulmonary tuberculosis history
• Active, diagnosed, or suspected autoimmune disease (including but not limited to: uveitis, enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma)
• Interstitial lung disease history or non-infectious pneumonia requiring oral or intravenous steroid therapy
• Long-term systemic hormone therapy (dose > 10mg prednisone/day) or any other form of immunosuppressive therapy
• Myocardial ischemia or myocardial infarction above grade II, hypertension and inability to reach the normal range after medication (systolic blood pressure >140mmHg, diastolic blood pressure >90mmHg)
• Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg<2g/L); history of gastrointestinal bleeding within 6 months; obvious bleeding tendency or undergoing thrombolytic or anticoagulant treatment
• Pregnant or lactating women
• Patients who participated in other clinical trials within 1 month
• Active infections which require systemic treatment
• HIV positive
• Other factors that may affect patients' safety or compliance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Camrelizumab plus apatinib	Drug: Camrelizumab plus apatinib; Camrelizumab 200mg q2w iv and apatinib 250mg qd po.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective remission rate	The proportion of patients with CR, PR, and SD in the group	From enrollment to disease progression, up to 6 months
Recurrence-free survival	The period from enrollment surgery to recurrence of HCC	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The survival rate in a year	1 year
Time to progress	The period from enrollment to disease progression	From enrollment to disease progression, up to 6 months
Adverse effect	Any adverse effects occur during the project	1 year

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Huashan Hospital; West China Hospital; The First Affiliated Hospital of Zhengzhou University; The First Hospital of Jilin University; Third Affiliated Hospital, Sun Yat-Sen University; Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Tianjin First Central Hospital; Shulan (Hangzhou) Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 16, 2019
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: July 20, 2019
• First Submitted That Met QC Criteria: July 26, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Actual): July 29, 2019
• Last Update Submitted That Met QC Criteria: July 26, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Liver transplantation; HCC; Apatinib; Camrelizumab
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: KY2019-SHR-APA-ZJU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No