Rituximab Combined With Prior Therapy in Advanced Hepatocellular Carcinoma: Efficacy & Safety Study

Phase 2

Recruiting

• Conditions: Advanced Hepatocellular Carcinoma
• Interventions: Drug: Rituximab+PD-1 or PD-L1 inhibitors+targeted therapy

• Registration Number: NCT06301399
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

Evaluation of the efficacy and safety of adding rituximab after failure of target immunotherapy in the Posterior treatment of advanced hepatocellular carcinoma

Detailed Description

Evaluation of the efficacy and safety of adding rituximab after failure of target immunotherapy in the Posterior treatment of advanced hepatocellular carcinoma

Study Timeline

• Status Verified: 2024-02
• Study First Submitted: 2024-02-16
• Study First Submitted QC: 2024-03-03
• Study First Posted: 2024-03-08
• Study Start: 2024-03-20
• Last Update Submitted: 2024-11-17
• Last Update Posted: 2024-11-20
• Primary Completion: 2025-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• 1)written informed consent signed prior to enrolment.
• 2. Age 17-79 years old (including boundary), male or female;
• 3. Subjects with histologically or cytologically confirmed advanced hepatocellular carcinoma (HCC), or clinical diagnosis that meets the American Association of Liver Diseases (AASLD) diagnostic criteria for hepatocellular carcinoma
• 4. Previous progression or intolerance after failure to target, immunization, or conventional therapy (including TKI, ICI, chemotherapy, VEGF monoclonal antibody, or ICI combined with TKI/VEGF monoclonal antibody/chemotherapy)
• 5. 2 weeks after the end of previous systemic therapy ≥ the first dose of this study, and the treatment-related AEs recovered to NCI-CTCAE ≤ Grade 1 (except for alopecia)
• 6. Child-Pugh liver function rating within 7 days prior to the first dose of the study drug: A grade and good B grade (≤ 7 points)
• 7. Phase B or C as assessed by BCLC or Phase III as assessed by CNLC
• 8. At least one measurable target lesion as assessed by the investigator according to the requirements of mRECIST v1.1 within 4 weeks prior to the first dose
• 9. Have adequate organ function (without receiving blood transfusion, erythropoietin, granulocyte colony-stimulating factor, albumin, or other medical support within 14 days prior to initiation of study drug therapy)
• 10. If the patient has HBsAg(+) or HBcAb(+), HBV-DNA must be < 2500 copies/mL or < 500 IU/mL or < upper limit of normal (ULN) to be enrolled, and those with elevated HBV-DNA must agree to receive nucleoside anti-hepatitis B virus therapy. Subjects who are negative for HCV antibody (-) or HCV-RNA are allowed to enroll, if HCV-RNA is positive, they need to agree to receive local standard standard antiviral therapy, and subjects must have ALT, AST, ≤ 3×ULN to enroll, and subjects with hepatitis B and C co-infection need to be excluded (HBV-DNA and HCV-RNA are positive)
• 11. Patients with cured hepatitis C are acceptable, and the lower limit of detection of HCV RNA < test center before starting study drug treatment
• 12. ECOG PS score: 0-1
• 13. Expected survival ≥ 12 weeks
• 14. Male or female of childbearing potential who are willing to use contraception in the trial, and females of childbearing potential must have a pregnancy test within 7 days prior to the first dose with a negative result
• 15)CD20 positive and CD20 scattered (non aggregated) distribution in tumors

Exclusion Criteria

• 1. Known hepatocholangiocarcinoma, mixed cell carcinoma, or fibrolamellar cell carcinoma
• 2. History of hepatic encephalopathy within 6 months prior to the first dose of this study
• 3. Portal hypertension with endoscopic red signs, or those who are considered by the investigator to have a high risk of bleeding or who have had esophageal or gastric variceal bleeding within 6 months before the first dose
• 4. Symptomatic brain or meningeal metastases (unless the patient has been >treated for 3 months, there is no evidence of progression in imaging results within 4 weeks before the first dose, and tumor-related clinical symptoms are stable)
• 5. The patient has human immunodeficiency virus (HIV) or active tuberculosis, or other uncontrolled active infection
• 6. Those who have undergone major surgery within 4 weeks before enrollment, and those who have had bone marrow biopsy, open biopsy, and intracranial biopsy within 7 days before screening
• 7. Those who have other malignant tumors in the past 5 years and have not been effectively controlled, except for carcinoma in situ of the cervix, squamous cell carcinoma of the skin or localized basal cell skin cancer
• 8. Known history of severe allergy to any monoclonal antibody or study drug excipient
• 9. Pregnant or lactating women
• 10. Other reasons judged by the investigator to be unsuitable for participating in this study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rituximab+PD-1 or PD-L1 inhibitors+targeted therapy	Rituximab+PD-1 or PD-L1 inhibitors+targeted therapy	Rituximab: Dissolve 375mg/m2 in 0.9% sodium chloride injection, dilute to a concentration of 1 mg/mL of rituximab, intravenous infusion every 3 weeks until tumor progression or intolerable toxic reactions occur. The recommended initial infusion rate is 50mg/h; After the initial 60 minutes, an increase of 50mg/h can be made every 30 minutes until the maximum speed is 400mg/h. The starting rate of rituximab infusion in the future can be 100mg/h, increasing by 100mg/h every 30 minutes until the maximum rate is 400mg/h. PD-1 (or PD-L1) inhibitors and targeted drugs: Select first-line PD-1 (or PD-L1) inhibitors and VEGFR targeted drugs according to clinical routine treatment, and administer according to the original first-line combination therapy dosage until progression or intolerable toxic reactions occur.

Primary Outcome Measures

Name	Time	Method
ORR	from the date of enrollment to death from any cause. (assessed up to 12 months）	mRESIST

Secondary Outcome Measures

Name	Time	Method
PFS	from the date of enrollment to death from any cause. (assessed up to 12 months）	mRESIST
OS	from the date of enrollment to death from any cause. (assessed up to 12 months）	mRESIST
DoR	from the date of enrollment to death from any cause. (assessed up to 12 months）	mRESIST
DCR	from the date of enrollment to death from any cause. (assessed up to 12 months）	mRESIST

Trial Locations

Locations (1)

Tianjin Medical University Cancer Institute & Hospital; 🇨🇳 Tianjin, Tianjin, China