GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Hepatocellular Carcinoma (HCC)

Hepatocellular Carcinoma Clinical Trial

Official title: Phase I Study of GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Hepatocellular Carcinoma (HCC)

Status Recruiting

Clinical Trial Summary

Background:

A new cancer treatment takes a person s own T cells, modifies them in a laboratory so they can better fight cancer cells, and then gives them back to the person. Researchers want to see if this treatment can help people with a certain type of liver cancer.

Objective:

To see if a personalized immune treatment, anti-GPC3 CAR-T cells, is safe.

Eligibility:

Adults aged 18 years and older who have Glypican-3 (GPC3) positive HCC, a type of liver cancer.

Design:

Participants will be screened with the following:

Blood and urine tests

Medical history

Physical exam

Heart function tests

Review of their symptoms and their ability to perform their normal activities

Tumor biopsy

Imaging scan of the chest, abdomen, and pelvis

Participants will have leukapheresis. They may have an IV (intravenous catheter, a small tube put into an arm vein) inserted into each arm or get a central line. Blood will be removed. A machine will separate the white blood cells from their blood. The rest of their blood will be returned to them.

Participants will be admitted to the hospital for about 2 weeks. They will get the chemotherapy drugs fludarabine and cyclophosphamide by IV for 3 days. Then they will receive the modified white blood cells by IV.

Participants will have frequent blood draws. They will give blood and tumor samples for research.

Participants will have follow-up visits for the next 15 years. Then they will be contacted by email or phone for the rest of their life. If their disease does not get worse after 5 years, they will continue to be invited to do imaging studies every 6 months.

Clinical Trial Description

Background:

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second leading cause of cancer-associated mortality with an average life expectancy of 6-9 months

Despite the success of several studies showing efficacy in treating HCC, most clinical trials have failed to prove a survival advantage.

Adoptive T-cell therapy exploits the natural ability of T-cells to recognize and eliminate their target.

GPC3 is a cell surface protein that is expressed in nearly all HCC yet is undetectable in normal adult hepatic tissues.

We want to evaluate the role of GPC3 targeted chimeric antigen receptor (CAR)-T cells in advanced GPC3 expressing HCC.

Objective:

To determine the safety and feasibility of T-cells, expressing a novel humanized anti-GPC3 chimeric antigen receptor, in participants with advanced HCC, expressing GPC3.

Eligibility:

Histologically confirmed diagnosis of hepatocellular carcinoma

GPC3 positivity of >= 25% by immunohistochemistry

At least 1 measurable lesion by RECIST v 1.1 criteria

Age >= 18 years

Design:

We plan to conduct a phase I dose escalation designed clinical trial using CAR (hYP7)-T cells in participants with GPC3 expressing advanced hepatocellular carcinoma.

Participants will undergo leukapheresis

Participants will receive a lymphocyte depleting chemotherapy conditioning regimen with the intent of enhancing the activity of the infused CAR-expressing T cells

Following the T cell infusion, there is a mandatory 9-day inpatient hospitalization to monitor for toxicity.

The participants will be closely monitored during the first year after cell infusion and followed for life. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Cancer
• Hepatocellular Carcinoma
• Liver Neoplasms
• Metastatic Hepatocellular Carcinoma

• NCT number: NCT05003895
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Donna M Hrones, C.R.N.P.
• Phone: (240) 858-3155
• Email: donna.mabry@nih.gov
• Status: Recruiting
• Phase: Phase 1
• Start date: December 8, 2021
• Completion date: December 31, 2025