A Single-arm, Non-randomized, Single-center Study to Evaluate Lenvatinib in Combination With Camrelizumab as First-Line Therapy in Patients With Advanced Hepatocellular Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- Camrelizumab
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Peking Union Medical College Hospital
- Enrollment
- 53
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a single arm, open-label, non-randomized and single-center phase I/II clinical study, to evaluate the the safety, tolerance and efficacy of Lenvatinib plus Camrelizumab as first-line therapy in patients with advanced Hepatocellular Carcinoma.
Detailed Description
The purpose of this study is to evaluate the safety, tolerance and efficacy of Lenvatinib combined with Camrelizumab as first-line therapy for patients with advanced hepatocellular carcinoma.The target sample size is 53.In the first phase 6 panticipants was evaluated (N=3+3), If there was no obvious dose-limiting toxicity (DLT), then entered the extended phase (N=47).Treatment continually until disease progression or intolerable toxicity or patients withdrawal of consent.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol;
- •Males or females, age ≥ 18 years at the time of informed consent;
- •Imaging (by AASLD or Standard for the diagnosis and treatment of primary liver cancer 2017 in China) or histopathologically or cytologically confirmed advanced HCC;
- •BCLC stage B or C, and not suitable for surgical or local therapy, or has progressed following surgical and/or local therapy;
- •No previous systematic treatment for HCC;
- •Have at least one measurable lesion (in accordance with RECIST v1.1); the measurable lesion has a long diameter ≥ 10 mm or lymphadenopathy has a short diameter ≥ 15 mm in spiral CT scan;
- •ECOG-PS score 0 or 1
- •Child-Pugh Class: Grade A
- •Life Expectancy of at least 3 months
- •Subjects with HBV infection: HBV DNA\<2000 IU/ml or \<10\^4 copy/mL, and have received anti-HBV therapy for at least 14 days prior to enrollment in the study, subjects with HCV-RNA(+) must receive antiviral therapy;
Exclusion Criteria
- •Hepatocellular carcinoma patients with any of the following:
- •Suitable for radical surgery; without an assessment lesion after radical surgery; liver transplantation history or ready for liver transplantation;
- •History of hepatic encephalopathy;
- •Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma;
- •Pregnant women (positive pregnancy test before taking medicine) or lactating women;
- •Known history of serious allergy to any monoclonal antibody or targeted anti-angiogenic drug (or any excipient);
- •Received any topical treatment within 4 weeks prior to the study, including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection;
- •Previous or existing CTCAE 5.0 standard grade 3 or above gastrointestinal fistula or non-gastrointestinal fistula (such as skin);
- •Factors to affect oral administration and absorption (such as inability to swallow, chronic diarrhea and intestinal obstruction);
- •Ascites with clinical symptoms (i.e. ascites with Child-Pugh rating \> 2) or cancerous ascites require therapeutic abdominal puncture or drainage. Or uncontrolled malignant ascites (ascites that researchers believe diuretics or puncture cannot control);
Arms & Interventions
Lenvatinib plus Camrelizumab
Camrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody. Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.
Intervention: Camrelizumab
Lenvatinib plus Camrelizumab
Camrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody. Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.
Intervention: Lenvatinib
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: one year
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients
Secondary Outcomes
- Overall Survival (OS)(one year)
- 3-months and 6-months Progression Free Survival Rate(6 months)
- Progression-free Survival (PFS)(one year)
- Duration of Response (DOR)(one year)
- Clinical Benefit Rate (CBR)(two years)
- 6-months and 1-year Mortality Rate(one year)
- Disease Control Rate (DCR)(one year)
- Adverse Events (AE)(two years)