Camrelizumab in Combination With Apatinib Plus NK Cell for Advanced HCC

NCT05171309 | Unknown Phase 2

• 1 other identifier: NFEC-2021-372
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of Camrelizumab in combination with apatinib plus NK cell in patients with advanced hepatocellular carcinoma.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular carcinoma; Camrelizumab; Apatinib; NK cell

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1

  From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)

Secondary Outcomes (6)

• The disease control rate (DCR)

  From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)

• The median progression free survival time (mPFS)

  From date of first dose of study drug to the date of first documentation of disease progression (up to approximately 3 years)

• The median overall survival time (mOS)

  From the start date of the Treatment Phase until date of death from any cause (up to approximately 3 years)

• Progression free survival rate at 12 months

  From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to approximately 3 years)

• Overall survival rate at 12 months

  From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to approximately 3 years)

Study Arms (1)

Camrelizumab in combination with apatinib plus NK cell

EXPERIMENTAL

Drug: Apatinib 250 mg once daily (QD) oral dosing. Other Names: • Apatinib Drug: Camrelizumab 200 mg intravenously every 2 weeks. Other Names: • Camrelizumab Drug: NK cell Cord blood derived NK cells 4 cycles, one cycle is defined as: total cells ≥1×109 per time, continuous intravenous infusion for 2 days every 14±2 days

Drug: Apatinib; Drug: Camrelizumab; Drug: NK cell

Interventions

Apatinib DRUG

250 mg once daily (QD) oral dosing.

Camrelizumab in combination with apatinib plus NK cell

Camrelizumab DRUG

200 mg intravenously every 2 weeks.

Camrelizumab in combination with apatinib plus NK cell

NK cell DRUG

Cord blood derived NK cells 4 cycles, one cycle is defined as: total cells ≥1×109 per time, continuous intravenous infusion for 2 days every 14±2 days

Camrelizumab in combination with apatinib plus NK cell

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 ≤ 70, male or female;
• Clinical or pathologically confirmed BCLC B (tumor numbers ≥ 4) or C stage hepatocellular carcinoma (except intracranial metastasis);
• At least one intrahepatic evaluable tumor existed, intrahepatic tumor is the primary tumor burden (according to RECIST v1.1, the long diameter of spiral CT scan of the measurable lesion is ≥ 10 mm or the short diameter of enlarged lymph nodes is ≥ 15 mm);
• No previous systematic (including systematic study drugs) HCC treatment;
• No contraindications of carrizumab, apatinib and NK cell therapy;
• Patients who have previously received local treatment (such as microwave ablation, radiofrequency ablation, absolute ethanol or acetic acid injection, cryoablation, high intensity focused ultrasound, transcatheter arterial chemoembolization or perfusion chemotherapy, etc.), A. if the focus has not received local treatment before, it can be used as the target focus; b. If the focus has received local treatment before, it can be used as the target focus after the progress is evaluated according to RECIST v1.1 standard;
• Child-Pugh score small or equal to 7 points (Child-Pugh A-B);
• Life expectancy of at least 12 weeks;
• ECOG score: 0 to 1 (according to the ECOG score classification);
• The subjects voluntarily joined the study, signed the informed consent form, had good compliance and cooperated with the follow-up;
• For female that non-surgical sterilization or in childbearing age need to use a medically approved contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period; For female that non-surgical sterilization or in childbearing age must have a negative serum or urine HCG test within 72 hours prior to study enrollment; and must be nonlactating; for male patients whose partner in a childbearing age, effective methods of contraception should be given during the trial and at the end of Camrelizumab injection.
• The laboratory parameters meets the following requirements (no blood components and cell growth factors are allowed within 14 days before the first dose):
• Absolute neutrophil count ≥ 1.5 × 109 / L; Platelets ≥ 50 × 109 / L; Hemoglobin ≥ 80 g / L; Biochemical examination shall meet the following standards: TBIL \< 1.5 × ULN； ALT and AST \< 5 × ULN； Bun and Cr ≤ 1 × The clearance rate of ULN or endogenous creatinine ≥ 50ml / min (Cockcroft Gault formula).
• Stable coagulation function: INR ≤ 1.5, PTT \< 1.2 times the upper limit of normal value (except for tumor related anticoagulant therapy).
• Anti HBV therapy should be initiated before enrollment for patients with detectable HBV DNA.

You may not qualify if:

• Accepted any systematic treatment before (excluding traditional Chinese medicine and traditional Chinese medicine preparations);
• Existed Hepatobiliary carcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrous lamellar cell carcinoma; Active malignant tumors other than HCC within 5 years or at the same time. Limited localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostate cancer in situ, in situ carcinoma of the cervix, and breast cancer in situ, can be included.
• History of organ allograft;
• Moderate and severe ascites with clinical symptoms, i.e. those who need therapeutic puncture and drainage, or child Pugh score \> 2 (except those who only show a small amount of ascites on imaging but are not accompanied by clinical symptoms); Uncontrolled or moderate pleural effusion and pericardial effusion;
• With a history of gastrointestinal bleeding or definite tendency of gastrointestinal bleeding within 6 months before enrollment, such as bleeding risk or severe esophageal and gastric varices, local active gastrointestinal ulcer lesions, and positive continuous fecal occult blood, shall not be included in the group (if fecal occult blood is positive in the baseline period, it can be rechecked. If it is still positive after recheck, gastroduodenoscopy is required (EGD), if EGD indicates the risk of bleeding, esophageal and gastric varices cannot be included in the group);
• Abdominal fistula, gastrointestinal perforation or abdominal abscess occurred within 6 months before the start of the study drug;
• Events of arterial/venous thrombosis occurring within the first 6 months of enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• Aspirin (\> 325 mg / day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel and cilostazol were currently or recently used (within 10 days before the start of study treatment);
• hrombosis or embolism events occurred within 6 months before the start of the study drug, such as cerebrovascular accidents (including transient ischemic attack, intracerebral hemorrhage, cerebral infarction), pulmonary embolism, etc;
• Suffering heart diseases with clinical symptoms or those not well controlled, such as: (1) heart failure in NYHA class 2 or higher; (2) unstable angina; (3) myocardial infarction occurred within 1 year; (4) clinically symptomatic supraventricular or ventricular arrhythmia requiring treatment or intervention; (5) Tc \> 450ms (male); QTc \> 470ms (female);
• Suffering from hypertension, and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥90 mmHg);
• Major vascular diseases (e.g., aortic aneurysms requiring surgical repair or recent peripheral arterial thrombosis) occurred within 6 months before the start of the study drug;
• Severe, unhealed or cracked wounds and active ulcers or untreated fractures;
• Major surgical treatment (except diagnosis) within 4 weeks before the start of study treatment or major surgical treatment is expected during the study period;
• Inability to swallow tablets, malabsorption syndrome, or any condition affecting gastrointestinal absorption;

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

apatinib; camrelizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Jinzhang Chen, MD.

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guosheng Yuan, PhD.

CONTACT

86-20-62787430; guoshengyuan1991@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 26, 2021
• First Posted: December 28, 2021
• Study Start: January 1, 2021
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2023
• Last Updated: December 28, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)