Checkpoint Inhibitor Combinations Therapy as First Line for HCC Via IT

NCT06482801 | Recruiting Phase 2 FDA Drug

• 1 other identifier: ZZ-IT-ICI-HCC 1line-023
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is designed to investigate the safety, response rates and survival outcomes of patients with hepatocellular carcinoma by infusion of CTLA4, PD1 and PDL1 antibodies combination with chemodrug or/and bevacizumab through intra-tumor (IT).

Conditions

Liver Cancer; Antibody

Keywords

Hepatocellular Carcinoma; Intra-tumor injection; First line; CTLA4 antibody; PD1 antibody; PDL1 antibody; chemodrug; anti-angiogenesis

Outcome Measures

Primary Outcomes (4)

• Safety of IT delivery of drugs combination treatment

  Safety will be assessed by recording all types of advise effects upon and after the treatment.

  5 years

• Progression-free survival

  Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented disease progression (as per RECIST 1.1) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment.

  5 years

• Disease control rate

  Disease control rate will be defined as objective response rate + steady disease rate.

  5 years

• Duration of remission (DOR)

  DOR will be defined as the duration of the cancer remission.

  5 years

Secondary Outcomes (1)

• Overall survival

  5 years

Study Arms (3)

IT injection of double ICI

EXPERIMENTAL

Arm 1: intra-tumor injection of double ICIs only.

Drug: ipilimumab+pembrolizumab or ipilimumab+durvalumab, idarubicin, bevacizumab

IT injection of double ICI and chemodrug

EXPERIMENTAL

Arm 2: intra-tumor injection of double ICIs and a chemodrug.

Drug: ipilimumab+pembrolizumab or ipilimumab+durvalumab, idarubicin, bevacizumab

IT injection of double ICI and chemodrug plus bevacizumab

EXPERIMENTAL

Arm 3: intra-tumor injection of double ICIs, a chemodrug, and bevacizumab.

Drug: ipilimumab+pembrolizumab or ipilimumab+durvalumab, idarubicin, bevacizumab

Interventions

ipilimumab+pembrolizumab or ipilimumab+durvalumab, idarubicin, bevacizumab DRUG

This study has 3 subgroups: Arm 1. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab is administrated with a total dose of 1-2mg/kg via intra-tumor fine needle injection in 10 min, every 3 weeks. Arm 2. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin is administrated via intra-tumor fine needle injection in 15 min, every 3 weeks. Arm 3. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin plus bevacizumab is administrated via intra-tumor fine needle injection in 20 min, every 3 weeks.

Also known as: Local ICIs.

IT injection of double ICI; IT injection of double ICI and chemodrug; IT injection of double ICI and chemodrug plus bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cytohistological confirmation is required for diagnosis of cancer.
• Signed informed consent before recruiting.
• Age above 18 years with estimated survival over 3 months.
• Child-Pugh class A or B/Child score \> 7; ECOG score \< 2
• Tolerable coagulation function or reversible coagulation disorders
• Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR \< 2.3 or PT \< 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin \> 28 g/L；Total bilirubin \< 51 μmol/L
• At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.
• Birth control.
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

You may not qualify if:

• Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
• Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
• Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
• Patients accompanied with other tumors or past medical history of malignancy;
• Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
• Patients have poor compliance.
• Any contraindications for hepatic arterial infusion procedure:
• A.Impaired clotting test (platelet count \< 60000/mm3, prothrombin activity \< 50%).
• B.Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C.Known severe atheromatosis. D.Known uncontrolled blood hypertension (\> 160/100 mm/Hg).
• Allergic to contrast agent;
• Any agents which could affect the absorption or pharmacokinetics of the study drugs
• Other conditions that investigator decides not suitable for the trial.

Sponsors & Collaborators

• Second Affiliated Hospital of Guangzhou Medical University: lead

Study Sites (1)

Second Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510260, China

RECRUITING

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Idarubicin; Bevacizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Zhenfeng Zhang, MD, PhD

  Second Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenfeng Zhang, MD, PhD

CONTACT

+862039195966; zhangzhf@gzhmu.edu.cn

Bingjia He, MD

CONTACT

+862039195965; 464677938@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2024
• First Posted: July 1, 2024
• Study Start: June 10, 2024
• Primary Completion (Estimated): December 30, 2030
• Study Completion (Estimated): December 30, 2035
• Last Updated: July 1, 2024

Record last verified: 2024-06

Locations

CN (1)