Clinical trial NCT04985136: A Study of Camrelizumab Combined With Rivoceranib Mesylate Versus Investigator's Choice of Regimen in Treatment of Patients With Advanced Hepatocellular Carcinoma (HCC)
Official title: A Randomized, Open-Label, Controlled, International Multi-Center Phase III Clinical Study of Camrelizumab Combined With Rivoceranib (Apatinib) Mesylate Versus Investigator's Choice of Regimen in Treatment of Patients With Hepatocellular Carcinoma (HCC) Who Have Been Treated With Immune Checkpoint Inhibitors (ICIs)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Advanced Hepatocellular Carcinoma (HCC)
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-02
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized，Open，Controlled, International Multi-Center
Primary purpose: TREATMENT

Brief summary: This is a randomized, open-label, international, multi-center, phase III trial to evaluate the efficacy and safety of Camrelizumab Combined with Rivoceranib Mesylate versus Investigator's Choice of Regimen in Treatment of Patients with Hepatocellular Carcinoma (HCC)


Eligibility criteria: Inclusion Criteria:

1. Subject must participate voluntarily and sign the informed consent form;
2. Aged ≥ 18 years old, male or female;
3. Histopathologically confirmed hepatocellular carcinoma;
4. Has PD on treatment with prior anti-PD-1/PD-L1/CTLA-4 monoclonal antibody (mAb) administered either as monotherapy or as combination therapy.
5. No more than 2 lines of previous system treatment;
6. Be able to provide fresh or archived tumor tissue samples;
7. Patient with at least one measurable lesion (for Stage I);
8. Barcelona clinic liver cancer: Stage B or C;
9. Child-Pugh score: ≤ 7;
10. ECOG PS score of 0-1;
11. Life expectancy of ≥ 12 weeks;
12. Adequate organ function
13. Must take one medically approved contraceptive measure

Exclusion Criteria:

1. Patients with any active, known or suspected autoimmune disorder;
2. Patients who have used corticosteroids or other immunosuppressive agents for systemic treatment within 1 month prior to randomization;
3. With known severe allergic reactions to any other monoclonal antibodies;
4. Received previous camrelizumab or rivoceranib mesylate treatment;
5. Patients who discontinued ICIs treatment due to immune-related toxicity;
6. Patients with known CNS metastasis or hepatic encephalopathy;
7. Patients with liver tumor burden greater than 50% of total liver in volume, or patients who have previously undergone liver transplantation;;
8. Patients with symptomatic ascites or pleural effusion requiring paracentesis and drainage, or patients who have undergone ascites or pleural effusion drainage within 2 weeks before randomization;
9. Patients with other malignancies currently or within the past 5 years;
10. Patients with hypertension which cannot be well controlled by antihypertensives; history of hypertensive crisis or hypertensive encephalopathy;
11. Uncontrolled cardiac diseases or symptoms；
12. Known hereditary or acquired bleeding disorders;
13. Clinically significant bleeding symptoms or clear bleeding tendency;
14. Patients with gastrointestinal perforation or gastrointestinal fistula;
15. Patients with significant vascular invasions with a high possibility of fatal bleeding;
16. Patients with important arterial/venous thrombosis;
17. Patients experiencing toxicity caused by previous anti-tumor therapy that has not recovered to Grade ≤ 1;
18. Patients with active infection;
19. Patients with congenital or acquired immune deficiency;
20. Patients who received live vaccines within 28 days prior to randomization, or are expect to be vaccinated during the treatment period;
21. Patients with other potential factors that may affect the study results.

Primary outcomes:
measure: Stage I：Objective Response Rate（ORR）
timeFrame: 2.5 years
measure: Stage II：Overall survival （OS）
timeFrame: 2.5 years
Secondary outcomes:
measure: Stage I：Overall survival （OS）
timeFrame: 2.5 years
measure: Adverse Events（AEs）
timeFrame: 2.5 years
measure: Stage II：Objective Response Rate（ORR）
timeFrame: 2.5 years
measure: Disease Control Rate（DCR）
timeFrame: 2.5 years
measure: Duration of Response（DoR）
timeFrame: 2.5 years
measure: Progression-Free-Survival （PFS）
timeFrame: 2.5 years
measure: time to progression （TTP）
timeFrame: 2.5 years
measure: Pharmacokinetics (PK) Ctrough of camrelizumab
timeFrame: 2.5 years
measure: Pharmacokinetics (PK) Ctrough of Apatinib
timeFrame: 2.5 years
measure: Proportion of anti- camrelizumab antibody (ADA)
timeFrame: 2.5 years
measure: Proportion of neutralizing antibody (Nab)
timeFrame: 2.5 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
References: