Ignite Creation Date:
2025-12-24 @ 2:10 PM
Ignite Modification Date:
2025-12-27 @ 9:38 PM
Study NCT ID:
NCT06968195
Status:
SUSPENDED
Last Update Posted:
2025-12-24
First Post:
2025-05-05
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Autologous CAR T Cells Targeting GPC3 (RPCAR01) for the Treatment of Advanced or Metastatic GPC3 Expressing Hepatocellular Carcinoma
Sponsor:
Roswell Park Cancer Institute
Organization:
Study Overview
Official Title:
A Phase I Clinical Trial Investigating Autologous CAR T Cells Targeting GPC3 in Relapsed or Refractory Hepatocellular Carcinoma
Status:
SUSPENDED
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
awaiting agreement with Sponsor
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
Detailed Description:
PRIMARY OBJECTIVE:
I. To assess the safety, toxicity, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of autologous genetically modified CAR T cells administered as a single infusion targeting GPC3 in adult patients with advanced or metastatic GPC3 expressing hepatocellular carcinoma.
SECONDARY OBJECTIVE:
I. To assess anti-tumor activity and in vivo persistence of adoptively transferred CAR T cells.
EXPLORATORY OBJECTIVES:
I. To assess serial serum cytokine levels and C-reactive protein (CRP) levels following CAR T cell infusions.
II. To identify biomarkers associated with treatment response. III. To investigate the milieu of the tumor microenvironment pre and post exposure to CAR T cell therapy.
IV. To assess circulating tumor-derived deoxyribonucleic acid (Ct DNA) levels pre and post CAR T cell therapy.
V. To assess circulating CAR T cell expansion and persistence.
OUTLINE: This is a dose escalation study of anti-GPC3-CAR autologous T lymphocytes (RPCAR01) CAR T cell.
Patients undergo leukapheresis within 28 days prior to RPCAR01 CAR T cell infusion. Patients then receive cyclophosphamide intravenously (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 echocardiography (ECHO) or multigated acquisition (MUGA) during screening and blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may also optionally undergo tissue sample collection throughout the trial.
After completion of study treatment, patients are followed up at days 2, 3, 4, 5, 6, 7, 14, and 28, months 2, 4, 6, 8, 10, and 12, and then as per separate long term follow up study for up to 15 years.
I. To assess the safety, toxicity, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of autologous genetically modified CAR T cells administered as a single infusion targeting GPC3 in adult patients with advanced or metastatic GPC3 expressing hepatocellular carcinoma.
SECONDARY OBJECTIVE:
I. To assess anti-tumor activity and in vivo persistence of adoptively transferred CAR T cells.
EXPLORATORY OBJECTIVES:
I. To assess serial serum cytokine levels and C-reactive protein (CRP) levels following CAR T cell infusions.
II. To identify biomarkers associated with treatment response. III. To investigate the milieu of the tumor microenvironment pre and post exposure to CAR T cell therapy.
IV. To assess circulating tumor-derived deoxyribonucleic acid (Ct DNA) levels pre and post CAR T cell therapy.
V. To assess circulating CAR T cell expansion and persistence.
OUTLINE: This is a dose escalation study of anti-GPC3-CAR autologous T lymphocytes (RPCAR01) CAR T cell.
Patients undergo leukapheresis within 28 days prior to RPCAR01 CAR T cell infusion. Patients then receive cyclophosphamide intravenously (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 echocardiography (ECHO) or multigated acquisition (MUGA) during screening and blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may also optionally undergo tissue sample collection throughout the trial.
After completion of study treatment, patients are followed up at days 2, 3, 4, 5, 6, 7, 14, and 28, months 2, 4, 6, 8, 10, and 12, and then as per separate long term follow up study for up to 15 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?: