A Study of Camrelizumab Combined Apatinib in Hepatocellular Carcinoma Previously Treated With Immune Checkpoint Inhibitors (ICIs).

Camrelizumab Combined Apatinib in Patients With Hepatocellular Carcinoma Previously Treated With Immune Checkpoint Inhibitors: A Single-Arm, Open-Label, Phase II Study.

The purpose of this study is to observe and preliminary explore the efficacy and safety of the combination of Camrelizumab and Apatinib regimen in treating advanced hepatocellular carcinoma (HCC) participants who have progressed following prior Immune Checkpoint Inhibitors (ICIs) treatment.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Immune Checkpoint Inhibitors
• Intervention / Treatment: Drug: Camrelizumab combined Apatinib regimen

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shanzhi Gu, MD; Phone Number: +86-731-88651900; Email: gushanzhi@hnca.org.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Shaozhi Gu, MD; Email: gushanzhi@hnca.org.cn
      • Principal Investigator: Shaozhi Gu, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 years old, both genders.
• Conform to the clinical diagnosis histological or cytological confirmation of HCC(hepatocellular carcinoma) and with at least one measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST 1.1.
• Liver function status Child-Pugh score less than or equal to 7.
• Barcelona Clinic Liver Cancer stage Category B or C.
• Disease progression following prior Immune Checkpoint Inhibitors (PD-1/PD-L1 or CTLA4 inhibitors) treatment for HCC, for at least 2 consecutive treatment cycles. Receipt of no more than 2 prior systemic therapies for advanced HCC.
• Eastern Cooperative Oncology Group Performance Status of 0 or 1.
• Life expectancy of at least 12 weeks.
• Adequate bone marrow, liver and renal function (without blood transfusion, without growth factor or blood components support within 14 days before enrollment).

Exclusion Criteria:

• 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.
• The prior ICIs treatments were discontinued by intolerable adverse events.
• Known or occurrence of central nervous system (CNS) metastases or hepatic encephalopathy.
• Patients with tumor burden ≥50% of the liver volume or received liver transplantation.
• Patients with clinical symptoms of ascites.
• 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.
• 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.
• previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency, such as: esophageal varices, local active ulcerative lesions, gastric ulcer and duodenal ulcer, the ulcerous colitis, gastrointestinal diseases such as portal hypertension or resection of tumor with bleeding risk, etc.
• Proteinuria ≥ (++) and 24 hours total urine protein > 1.0 g.
• 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.
• Prior Camrelizumab or Apatinib treatments.

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+Apatinib	Drug: Camrelizumab combined Apatinib regimen; Camrelizumab 200mg iv every 2 weeks; Apatinib,250 mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).	Up to approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival(PFS)	Progression-free survival(PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).	Up to approximately 12 months
Time to objective response(TTR)	Time to objective response(TTR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	Up to approximately 12 months
Duration of Response (DoR)	Duration of Response (DoR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).	Up to approximately 12 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).	Up to approximately 12 months
6-month survival rate	6-month survival rate	Up to approximately 12 months
9-month survival rate	9-month survival rate	Up to approximately 12 months
12-month survival rate	12-month survival rate	Up to approximately 12 months
Overall survival(OS)		Up to approximately 24 months
Safety as measured by the rate of AEs, SAEs and laboratory abnormalities	Safety as measured by the rate of AEs, SAEs 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

Collaborators and Investigators

• Sponsor: Hunan Cancer Hospital
• Collaborators: Jiangsu Hengrui Pharmaceuticals Co.,Ltd

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2021
• Primary Completion (Anticipated): March 2, 2022
• Study Completion (Anticipated): August 30, 2023

Study Registration Dates

• First Submitted: March 29, 2021
• First Submitted That Met QC Criteria: March 29, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 1, 2021
• Last Update Submitted That Met QC Criteria: March 29, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: SHR-1210-IIT-HCC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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