RECRUITING

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

Conditions

Hepatocellular Carcinoma Hepatocellular Cancer Metastatic Hepatocellular Carcinoma immuno therapy Targeted Therapy Leukapheresis Gene Therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-12-08

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05003895

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histopathological confirmation of HCC by the NCI Laboratory of Pathology * Participants must: * have progressed on the prior first line of standard therapy * 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 investigators. * Tumor must have GPC3 positivity of \>= 25% by immunohistochemistry on freshly collected biopsy * Participants must have at least 1 measurable lesion by RECIST version 1.1 * Participants must have a disease that is not amenable to potentially curative resection, ablation, or transplantation. * Age \>= 18 years. * Performance status (ECOG) 0-1 * Participants must have adequate organ and marrow function as defined below: * Normal cardiac ejection fraction (\>= 50% by echocardiogram) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 4 weeks before treatment initiation. * Room air oxygen saturation of 92% or greater. * Treatment-related toxicities must be resolved to \<= grade 1. * For participants with brain metastases: Participants with \<=3 (three or fewer) brain metastases that have been treated with surgery or stereotactic radiosurgery or other form of treatment are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. * The study drugs are harmful to developing human fetus. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) at the study entry, for the duration of study therapy, and up to 180 days after the last dose of the study drug(s). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. * HBV infected participants must be on antivirals and have HBV DNA \< 100IU/mL. HCV infected participants can be enrolled with close HCV RNA level monitoring. * Participants must be able to understand and be willing to sign a written informed consent. * For participants that do not have a legally authorized representative in place, one must be identified before study treatment starts	* Prior systemic therapy, an investigational therapy, radiation, and/or surgery within 4 weeks prior to treatment initiation. * Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with an infusion of CAR-T cells within 8 weeks prior to treatment initiation. * Child-Pugh class B or C liver function * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Participants who require anticoagulation (e.g. warfarin) or anti-platelet therapy (e.g. aspirin \> 325 mg/day or clopidogrel). * Any form of primary immunodeficiency (e.g. severe combined immunodeficiency). * HIV-positive participants are excluded because HIV causes complicated immune deficiency and study treatment can pose more risks for these participants. * Participants with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to participants with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or CIDP, myasthenia gravis; systemic autoimmune diseases such as SLE, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn s, ulcerative colitis, hepatitis; and participants with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome. * History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine. * Hospitalization within 7 days prior to treatment initiation. * Systemic corticosteroid therapy of any dose within 14 days prior to the treatment initiation. Corticosteroid creams, ointments, and eye drops are allowed. * Pregnant women are excluded from this study because study therapy can cause fetal harm. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with study therapy, breastfeeding should be discontinued if the mother is treated with study drugs. * Participants who received live or attenuated vaccine or virus-based vaccine within 30 days before initiation of study therapy * Participants with a history of seizure disorder * Participants with an expected life expectancy of less than 3 months before initiation of study therapy.

Inclusion Criteria

Exclusion Criteria

* Histopathological confirmation of HCC by the NCI Laboratory of Pathology
* Participants must:
* have progressed on the prior first line of standard therapy
* 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 investigators.
* Tumor must have GPC3 positivity of \>= 25% by immunohistochemistry on freshly collected biopsy
* Participants must have at least 1 measurable lesion by RECIST version 1.1
* Participants must have a disease that is not amenable to potentially curative resection, ablation, or transplantation.
* Age \>= 18 years.
* Performance status (ECOG) 0-1
* Participants must have adequate organ and marrow function as defined below:
* Normal cardiac ejection fraction (\>= 50% by echocardiogram) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 4 weeks before treatment initiation.
* Room air oxygen saturation of 92% or greater.
* Treatment-related toxicities must be resolved to \<= grade 1.
* For participants with brain metastases: Participants with \<=3 (three or fewer) brain metastases that have been treated with surgery or stereotactic radiosurgery or other form of treatment are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment.
* The study drugs are harmful to developing human fetus. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) at the study entry, for the duration of study therapy, and up to 180 days after the last dose of the study drug(s). Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
* HBV infected participants must be on antivirals and have HBV DNA \< 100IU/mL. HCV infected participants can be enrolled with close HCV RNA level monitoring.
* Participants must be able to understand and be willing to sign a written informed consent.
* For participants that do not have a legally authorized representative in place, one must be identified before study treatment starts

* Prior systemic therapy, an investigational therapy, radiation, and/or surgery within 4 weeks prior to treatment initiation.
* Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with an infusion of CAR-T cells within 8 weeks prior to treatment initiation.
* Child-Pugh class B or C liver function
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Participants who require anticoagulation (e.g. warfarin) or anti-platelet therapy (e.g. aspirin \> 325 mg/day or clopidogrel).
* Any form of primary immunodeficiency (e.g. severe combined immunodeficiency).
* HIV-positive participants are excluded because HIV causes complicated immune deficiency and study treatment can pose more risks for these participants.
* Participants with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. These include but are not limited to participants with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome or CIDP, myasthenia gravis; systemic autoimmune diseases such as SLE, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn s, ulcerative colitis, hepatitis; and participants with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome.
* History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.
* Hospitalization within 7 days prior to treatment initiation.
* Systemic corticosteroid therapy of any dose within 14 days prior to the treatment initiation. Corticosteroid creams, ointments, and eye drops are allowed.
* Pregnant women are excluded from this study because study therapy can cause fetal harm. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with study therapy, breastfeeding should be discontinued if the mother is treated with study drugs.
* Participants who received live or attenuated vaccine or virus-based vaccine within 30 days before initiation of study therapy
* Participants with a history of seizure disorder
* Participants with an expected life expectancy of less than 3 months before initiation of study therapy.

Contacts and Locations

Study Contact

Donna M Hrones, C.R.N.P.

CONTACT

(240) 858-3155

donna.mabry@nih.gov

Tim F Greten, M.D.

CONTACT

(240) 760-6114

gretentf@mail.nih.gov

Principal Investigator

Tim F Greten, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Tim F Greten, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-12-08

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2021-12-08

Study Completion Date2025-12-31

Terms related to this study

Keywords Provided by Researchers

immuno therapy
Targeted Therapy
Leukapheresis
Gene Therapy

Additional Relevant MeSH Terms

Hepatocellular Carcinoma
Hepatocellular Cancer
Metastatic Hepatocellular Carcinoma