NCT02932956

Brief Summary

This study enrolls patients who have GPC3-positive solid tumors currently. Patients may be considered if the cancer has come back, has not gone away after standard treatment or the patient cannot receive standard treatment. This research study uses special immune system cells called GAP T cells, a new experimental treatment. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting cancer: antibodies and T cells. Antibodies are types of proteins that protect the body from infectious diseases and possibly cancer. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including cells infected with viruses and tumor cells. Both antibodies and T cells have been used to treat patients with cancers. They have shown promise, but have not been strong enough to cure most patients. Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. In preclinical studies, the investigators made several genes called a chimeric antigen receptor (CAR), from an antibody called GC33 that recognizes glypican-3, a proteoglycan found on solid tumors including pediatric liver cancers (GPC3-CAR). This study will test T cells genetically engineered with a GPC3-CAR (GAP T cells) in patients with GPC3-positive solid tumors (currently only enrolling liver tumors). The GAP T cells are an investigational product not approved by the Food and Drug Administration. The purpose of this study is to find the biggest dose of GAP T cells that is safe, to see how long they last in the body, to learn what the side effects are and to see if the GAP T cells will help people with GPC3-positive solid tumors. This study enrolls patients who have GPC3-positive solid tumors (currently only enrolling liver tumors).

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1

Timeline
131mo left

Started Dec 2018

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress41%
Dec 2018Feb 2037

First Submitted

Initial submission to the registry

October 12, 2016

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 13, 2016

Completed
2.2 years until next milestone

Study Start

First participant enrolled

December 17, 2018

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 27, 2021

Completed
15.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2037

Expected
Last Updated

September 19, 2025

Status Verified

September 1, 2025

Enrollment Period

2.8 years

First QC Date

October 12, 2016

Last Update Submit

September 16, 2025

Conditions

Liver Cancer

Keywords

GPC3-CAR T cellsGPC3GlypicanLiver cancer

Outcome Measures

Primary Outcomes (1)

  • Number of Patients with Dose Limiting Toxicity

    A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the GPC3-CAR T cells. Specifically those which are Grade 5; non-hematologic Grade 3-4 not returning to Grade 2 within 72 hours; Grade 2-4 allergic reaction; Hematologic Grade 4 that fails to return to Grade 2 or baseline (whichever is more severe) within 14 days; all grade 4 CRS and neurologic toxicities and grade 3 CRS and neurologic toxicities that fail to return to Grade 1 within 7 days.

    6 weeks

Secondary Outcomes (2)

  • Percent of Patients with best response as either complete remission or partial remission

    6 weeks

  • Median T cell persistence

    15 years

Study Arms (1)

GAP T cells + Fludarabine and Cytoxan

EXPERIMENTAL

GPC3-Car (GAP T cells) along with lymphodepleting chemotherapy (Cytoxan and Fludarabine) will be administered to patients with GPC3-positive solid tumors.

Genetic: GAP T cellsDrug: CytoxanDrug: Fludara

Interventions

GAP T cellsGENETIC

Five different dosing schedules will be evaluated. Three to six patients will be evaluated on each dosing schedule. The following dose levels will be evaluated: DL1: 1x10\^7/m2 DL2: 3x10\^7/m2 DL3: 1x10\^8/m2 DL4: 3x10\^8/m2 DL5: 1x10\^9/m2 The doses are calculated according to the actual number of GPC3-CAR transduced T cells.

Also known as: GPC3-CAR T cells
GAP T cells + Fludarabine and Cytoxan
CytoxanDRUG

Cyclophosphamide will be given at a dose of 500 mg/m2/day for 3 days given intravenously.

Also known as: Cyclophosphamide
GAP T cells + Fludarabine and Cytoxan
FludaraDRUG

Fludarabine will be given at a dose of 30 mg/m2/day for 3 days given intravenously.

Also known as: Fludarabine
GAP T cells + Fludarabine and Cytoxan

Eligibility Criteria

Age1 Year - 21 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Relapsed or refractory GPC3-positive\* solid tumors (currently only enrolling liver tumors)
  • Age ≥ 1 year and ≤ 21 years
  • Lansky or Karnofsky score ≥60%
  • Life expectancy ≥16 weeks
  • Child-Pugh-Turcotte score \<7 (for patients with hepatocellular carcinoma only)
  • Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

You may not qualify if:

  • History of hypersensitivity reactions to murine protein-containing products OR presence of human anti-mouse antibody (HAMA) prior to enrollment (only patients who have received prior therapy with murine antibodies)
  • History of organ transplantation
  • Known HIV positivity
  • Active bacterial, fungal or viral infection (except Hepatitis B or Hepatitis C virus infections)
  • Severe previous toxicity from cyclophosphamide or fludarabine
  • Treatment Eligibility
  • Age ≥ 1 year and ≤ 21 years
  • Barcelona Clinic Liver Cancer Stage A, B or C (for patients with hepatocellular carcinoma only)
  • Life expectancy of ≥ 12 weeks
  • Lansky or Karnofsky score ≥ 60%
  • Child-Pugh-Turcotte score \< 7 (for patients with hepatocellular carcinoma only)
  • Adequate organ function:
  • Creatinine clearance as estimated by Cockcroft Gault or Schwartz ≥ 60 ml/min
  • serum AST\< 5 times ULN
  • total bilirubin \< 3 times ULN for age
  • +17 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Liver Neoplasms

Interventions

Cyclophosphamidefludarabine phosphatefludarabine

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • David Steffin, M.D.

    Baylor College of Medicine

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

October 12, 2016

First Posted

October 13, 2016

Study Start

December 17, 2018

Primary Completion

September 27, 2021

Study Completion (Estimated)

February 1, 2037

Last Updated

September 19, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations

US(1)