Neoadjuvant Intra-tumor Double Immunotherapy for Hepatocellular Carcinoma.

NCT06492408 | Recruiting Phase 2 FDA Drug

• 1 other identifier: ZZ-IT-ICIs-HCC-Neoadjuvant-027
• 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 delivery of CTLA4 and PD1 or PDL1 antibodies combination through CT-guided intra-tumor (IT) injection.

Conditions

Hepatic Cancer; Surgery

Keywords

Hepatocellular Carcinoma;; Intra-tumor injection; Neoadjuvant therapy; Surgery; Immunotherapy; CTLA4 antibody; PD1 antibody; PDL1 antibody

Outcome Measures

Primary Outcomes (2)

• pCR rate for the study groups

  Pathologic complete response (pCR) is defined as after neoadjuvant therapy, the surgical specimen can not find any residual cancer cells.

  Six months

• mPR rate for the study groups

  Major pathologic response (MPR) is defined as pathological less than 10% survival cancer cells after tumor resection.

  Six months

Secondary Outcomes (4)

• Toxicity of the study groups

  Six months

• Response rates to neoadjuvant treatment

  Six years

• Recurrence-free survival

  Six years

• Overall survival

  Six years

Study Arms (3)

Group 1: IT injection of double ICIs

EXPERIMENTAL

Neoadjuvant therapy: intra-tumor injection of double ICIs only.

Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

Group 2: IT injection of double ICIs and chemodrug

EXPERIMENTAL

Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug.

Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

Group 3: IT injection of double ICIs and chemodrug plus bevacizumab

EXPERIMENTAL

Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug plus bevacizumab.

Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

Interventions

ipilimumab, pembrolizumab, 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, total 3-4 times. Arm 2. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin is administrated via intra-tumor fine needle injection in 15 min, every 3 weeks, total 3-4 times. 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, total 3-4 times.

Also known as: Other ICIs

Group 1: IT injection of double ICIs; Group 2: IT injection of double ICIs and chemodrug; Group 3: IT injection of double ICIs 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:

• Histologically or cytologically confirmed previously untreated hepatocellular carcinoma (HCC). If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected HCC are eligible, but pathology must be confirmed prior to initiating treatment on study.
• The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
• Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
• Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L; Hemoglobin \>= 8.0 g/dL; Platelets \>= 100 x 10\^9/L; Total bilirubin =\< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin \< 3.0 mg/dL); Creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance \>= 50 mL/min.
• 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. 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)

The Second Affiliated Hospital of Guangzhou Medical University

Guanzhou, Guangdong, 51260, China

RECRUITING

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Ipilimumab; pembrolizumab; durvalumab; 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)

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

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2024
• First Posted: July 9, 2024
• Study Start: July 1, 2024
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2033
• Last Updated: July 9, 2024

Record last verified: 2024-07

Locations

CN (1)