Clinical trial NCT04035876: Combination Camrelizumab (SHR-1210) and Apatinib for Downstaging/Bridging of HCC Before Liver Transplant
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Hepatocellular Carcinoma
Liver Transplant
Keywords: Camrelizumab
Apatinib
HCC
Liver transplantation
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Shulan (Hangzhou) Hospital
name: West China Hospital
name: Huashan Hospital
name: Third Affiliated Hospital, Sun Yat-Sen University
name: The First Affiliated Hospital of Zhengzhou University
name: The First Hospital of Jilin University
name: Tianjin First Central Hospital
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
First posted: 2019-07-29
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective remission rate
timeFrame: From enrollment to disease progression, up to 6 months
measure: Recurrence-free survival
timeFrame: 1 year
Secondary outcomes:
measure: Overall survival
timeFrame: 1 year
measure: Time to progress
timeFrame: From enrollment to disease progression, up to 6 months
measure: Adverse effect
timeFrame: 1 year
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Medical School of Zhejiang University
state: Zhejiang
Study officials:
References: