Phase I Study of GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies
National Cancer Institute (NCI)
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 types of 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 solid tumor malignancy. 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.
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. * GPC3 is also expressed strongly in s…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Histopathological confirmation of HCC or other solid tumor malignancy by the NCI Laboratory of Pathology * Participants must: * have progressed on at least 1 prior line of treatment OR --been intolerant of at least 1 prior line of treatment. * Participants must have at least 1 focus of disease that is amenable to mandatory tumor biopsy prior to study treatment initiation to determine tumor GPC3 expression and be willing to undergo this. Ideally, the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the…
Interventions
- DrugCyclophosphamide
Daily x 3 doses on Day -3, -2, -1 300 mg/m2 IV infusion (200 mg/m\^2 in Dose Level -1)
- BiologicalCAR-T cell
Single infusion on Day 0
- DrugFludarabine
Daily x 2 doses on Day -2 and -1 30 mg/m\^2 IV infusion administered following cyclophosphamide
Location
- National Institutes of Health Clinical CenterBethesda, Maryland