Anti-GPC3 CAR-T for Treating GPC3-positive Advanced Hepatocellular Carcinoma (HCC)

Phase I Trial of Anti-GPC3 Chimeric T Cells for Subjects With GPC3-Positive Advanced Hepatocellular Carcinoma

The goal of this clinical trial is to evaluate the safety and efficacy of anti-GPC3 scFv-41BB-CD3ζ-tEGFR chimeric antigen receptor (CAR)-modified T (CAR-T) cells in treating patients with GPC3-positive advanced hepatocellular carcinoma (HCC).

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs; Drug: Fludarabine; Drug: Cyclophosphamide

Detailed Description

Primary Objectives:

1. To evaluate the safety of intravenous administration of the anti-GPC3 CAR-T cells in patients with HCC or lung squamous cell carcinoma
2. To access the safety of anti-GPC3 CAR-T cells in HCC patients through catheter injection

Secondary Objectives:

1. To evaluate the efficacy of anti-GPC3 CAR-T cells in patients with advanced HCC or lung squamous cell carcinoma
2. To monitor the serum cytokine and expression level of tumor markers such as AFP, CEA and GPC3
3. To assess the persistence in peripheral blood and intratumoral infiltration of anti-GPC3 CAR-T cells

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • ChongQing, Chongqing, China, 400037
      • Department of Oncology, Xinqiao Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Expected to survive more than 3 months
• PS 0-2
• Immunohistochemistry was confirmed to be GPC3 positive hepatocellular carcinoma
• Patients with no ability to receive TACE combined with sorafenib
• WBC>3.5×1e+9/L,Hb>90g/L,PLT>75×1e+9/L
• HBV DNA copy number less than 100/ml
• ALT≤5ULN, AST≤5ULN, TB≤1.5ULN, ALB≥35g/L
• Understand this test and have signed informed consent

Exclusion Criteria:

• Hepatic encephalopathy, autoimmune diseases, or any uncontrolled active disease that hinders participation in the trial
• Decompensated liver cirrhosis, liver function Child-pugh C grade
• Portal vein tumor thrombus, arterial portal fistula, hepatic arteriovenous
• Long-term use of immunosuppressive agents after organ transplantation
• Screening indicated that the target cell transfection rate was less than 30%
• Invasive pulmonary embolism, deep venous thrombosis, or other major arterial / venous thromboembolic events occurred 30 days or 30 days prior to randomization
• Subjects had an active or uncontrollable infection requiring systemic therapy 14 days or 14 days prior to randomization
• Pregnant or lactating subjects
• In the opinion of the investigator, the presence of a medical history or a history of mental state may increase the number of subjects associated with the risk factors associated with the study or study drug administration
• Subjects who have signed a written consent or who are in compliance with the study procedure; or who are unwilling or unable to comply with the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: anti-GPC3 CAR-T; Transcatheter arterial chemoembolization (TACE) combine with GPC3-CART infusion

Biological: Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs; transcatheter arterial chemoembolization + CAR-T infusion; Drug: Fludarabine; Fludarabine will be administered at dose of 25mg/m2/d; Drug: Cyclophosphamide; Cyclophosphamide will be administered at dose of 40mg/kg for 1 day and then fludarabine will be given for the next 5 days and then the T cells will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0	Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Overall complete remission rate defined by the standard response criteria	Overall complete remission rate defined by the standard response criteria	8 weeks
Persistence: Duration of CAR-positive T cells in circulation	Duration of CAR-positive T cells in circulation	6 months

Collaborators and Investigators

• Sponsor: Xinqiao Hospital of Chongqing

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2017
• Primary Completion (Anticipated): May 31, 2019
• Study Completion (Anticipated): May 31, 2020

Study Registration Dates

• First Submitted: March 5, 2017
• First Submitted That Met QC Criteria: March 17, 2017
• First Posted (Actual): March 20, 2017

Study Record Updates

• Last Update Posted (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: March 17, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: GPC3CAR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No