Neoadjuvant Intra-tumor Double Immunotherapy for Hepatocellular Carcinoma.

NCT ID: NCT06492408

Last Updated: 2024-07-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-01
• Study Completion Date: 2033-12-30

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.

Detailed Description

Antibodies against CTLA4, PD1 or PDL1 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration of the tumor, improve the efficacy, and reduce systemic adverse reactions. CTLA4 antibody ipilimumab has been widely effectively using to combine with PD1 or PDL1 antibody and this study is to combine ipilimumab and PD1 antibody or PDL1 antibody, so called double checkpoint inhibitors combination therapy, as neoadjuvant therapy for hepatocellular carcinoma (HCC) via intra-tumor admistration. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the double checkpoint inhibitors combination therapy for cancer patients as neoadjuvant treatment via intra-tumor delivery. This phase II clinical trial is designed to assess the safety and survival benefit of ipilimumab and pembrolizumab or durvalumab combination with or without chemodrug or bevacizumab as neoaduvant therapy on patients with HCC, including safety, pCR, mPR, PFS, ORR, DCR, and median survival time.

Conditions

Hepatic Cancer; Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1: IT injection of double ICIs

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

Group Type: EXPERIMENTAL

ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

Intervention Type: 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.

Group 2: IT injection of double ICIs and chemodrug

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

Group Type: EXPERIMENTAL

ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

Intervention Type: 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.

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

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

Group Type: EXPERIMENTAL

ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

Intervention Type: 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.

Interventions

ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab

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.

Intervention Type: DRUG

Other Intervention Names

Other ICIs

Eligibility Criteria

Inclusion Criteria

1. 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.

2. The patient must be a suitable candidate for surgery, in the opinion of the treating physician.

3. 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.

4. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1

5. 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.

6. Birth control.

7. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria

1. Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;

2. Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;

3. Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;

4. Patients accompanied with other tumors or past medical history of malignancy;

5. Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;

6. 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).

7. Allergic to contrast agent;

8. Any agents which could affect the absorption or pharmacokinetics of the study drugs

9. Other conditions that investigator decides not suitable for the trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital of Guangzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zhenfeng Zhang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Second Affiliated Hospital of Guangzhou Medical University

Locations

The Second Affiliated Hospital of Guangzhou Medical University

Guanzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhenfeng Zhang, MD, PhD

Role: CONTACT

zhangzhf@gzhmu.edu.cn

+862039195966

Bingjia He, MD

Role: CONTACT

464677938@qq.com

+862039195965

Facility Contacts

Zhenfeng Zhang, MD,PhD

Role: primary

zhangzhf@gzhmu.edu.cn

02034153532

Other Identifiers

ZZ-IT-ICIs-HCC-Neoadjuvant-027

Identifier Type: -

Identifier Source: org_study_id