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

• ClinicalTrials.gov Identifier: NCT03084380
• Recruitment Status: Unknown
• First Posted: March 20, 2017
• Last Update Posted: March 20, 2017
• Sponsor: Xinqiao Hospital of Chongqing
• Information provided by (Responsible Party): Qingzhu Jia, M.D., Xinqiao Hospital of Chongqing

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Biological: Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs; Drug: Fludarabine; Drug: Cyclophosphamide	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Trial of Anti-GPC3 Chimeric T Cells for Subjects With GPC3-Positive Advanced Hepatocellular Carcinoma
• Estimated Study Start Date: June 1, 2017
• Estimated Primary Completion Date: May 31, 2019
• Estimated Study Completion Date: May 31, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety: Measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0 [ Time Frame: 4 weeks ]
   Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0

Secondary Outcome Measures :

1. Efficacy: Overall complete remission rate defined by the standard response criteria [ Time Frame: 8 weeks ]
   Overall complete remission rate defined by the standard response criteria
2. Persistence: Duration of CAR-positive T cells in circulation [ Time Frame: 6 months ]
   Duration of CAR-positive T cells in circulation

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

China, Chongqing

Department of Oncology, Xinqiao Hospital

ChongQing, Chongqing, China, 400037

Sponsors and Collaborators

Xinqiao Hospital of Chongqing

More Information

• Responsible Party: Qingzhu Jia, M.D., Secretary of research, Xinqiao Hospital of Chongqing
• ClinicalTrials.gov Identifier: NCT03084380
• Other Study ID Numbers: GPC3CAR
• First Posted: March 20, 2017
• Last Update Posted: March 20, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Cyclophosphamide; Fludarabine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists