CAR T Cells for Liver Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must be taking: Antivirals

Must not be taking: Glucocorticoids

Disqualifiers: Child-Pugh B/C cirrhosis, Active bleeding, Alcohol abuse, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of RPCAR01 chimeric antigen receptor (CAR) T cells and to see how well it works in treating patients with GPC3 expressing hepatocellular carcinoma (HCC) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). In GPC3 expressing HCC cancerous cell tissue overexpresses, or makes too much of, a protein called "GPC3" on the surface of those cells (while only rarely expressed in healthy tissue). RPCAR01 is a genetically modified T cell (a part of the immune system) product that targets GPC3 and decreases the inhibition of T cells by a protein called transforming growth factor beta (TGFB). The drug is prepared by taking T cells from the blood by a procedure called "leukapheresis." The T cells are then modified to make them target GPC3 and disrupt TGFB which may help the body's immune system identify and kill GPC3 tumor cells. Lymphodepletion chemotherapy with cyclophosphamide and fludarabine involves receiving a short course of chemotherapy to kill T cells before receiving the RPCAR01 CAR T cell infusion. Giving RCAR01 CAR T cells may be safe, tolerable, and/or effective in treating patients with advanced or metastatic GPC3 expressing HCC.

Research Team

Anuradha Krishnamurthy

Principal Investigator

Roswell Park Cancer Institute

Eligibility Criteria

This trial is for patients with advanced or metastatic hepatocellular carcinoma (HCC) that overexpresses GPC3, a protein rarely found in healthy tissue. Participants must have HCC that has spread and are willing to undergo leukapheresis to provide T cells for treatment.

Inclusion Criteria

I've had 2 standard treatments for liver cancer, including immunotherapy and a drug like lenvatinib.

I have been diagnosed with liver cancer, not mixed with bile duct cancer.

My cancer can be measured and has grown or changed since last treatment.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have had recent bleeding that hasn't stopped.

My liver condition is severe (Child-Pugh B or C).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Leukapheresis

Patients undergo leukapheresis to collect T cells for modification

1 day

1 visit (in-person)

Lymphodepletion Chemotherapy

Patients receive cyclophosphamide and fludarabine to prepare for CAR T cell infusion

3 days

3 visits (in-person)

CAR T Cell Infusion

Patients receive RPCAR01 CAR T cells infusion

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Multiple visits at days 2, 3, 4, 5, 6, 7, 14, 28, months 2, 4, 6, 8, 10, 12

Long-term Follow-up

Participants are monitored for long-term outcomes and survival

Up to 15 years

Treatment Details

Interventions

• Anti-GPC3-CAR Autologous T Lymphocytes

Trial Overview The trial tests RPCAR01 CAR T cells, which are the patient's own immune cells modified to target GPC3 on cancer cells. It includes lymphodepletion chemotherapy with cyclophosphamide and fludarabine before infusing the modified T cells back into the patient.

Participant Groups

Group I: Treatment (RPCAR01 CAR T cells) Experimental Treatment 9 Interventions

Patients undergo leukapheresis within 28 days prior to RPCAR01 CAR T cell infusion. Patients then receive cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3 and RPCAR01 CAR T cells IV over 15 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA during screening and blood sample collection and CT or MRI throughout the trial. Patients may also optionally undergo tissue sample collection throughout the trial.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+