CAR-GPC3 T Cells in Patients With Refractory Hepatocellular Carcinoma

NCT03146234 | Completed DMC

• 1 other identifier: CG1006
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to determine the safety and efficacy of CAR-GPC3 T cells in patients with relapsed or refractory hepatocellular carcinoma. Single or multiple doses of GPC3-targeted CAR T cells will be given to subjects with unmet medical needs for which there are no effective therapies known at this time.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and tolerance

  Study related adverse events are defined as signs above CTCAE Grade 3, laboratory toxicities and clinical events occurred at any time from the first day of infusion to week 24 that are "possibly", "likely", or "definitely" related to the study, including infusion related toxicity and CAR-GPC3 T cells related toxicity. Include but not limited to: Fever; Chills; Nausea, vomiting and other gastrointestinal symptoms; Fatigue; Hypotension; Respiratory distress; Tumor lysis syndrome; Cytokine release syndrome; Neutropenia, thrombocytopenia; Liver and kidney dysfunction; Other toxicities.

  24 weeks

Secondary Outcomes (1)

• Engraftment

  2 years

Other Outcomes (1)

• Anti-tumor responses to CAR-GPC3 T cell infusions

  2 years

Study Arms (1)

CAR-GPC3 T cells

EXPERIMENTAL

Autologous T Cells with a GPC3-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection. Lymphodepletion conditioning regimen: A combination of fludarabine and cyclophosphamide will be administered at Day -6 to Day -3 prior to CAR-GPC3 T cells infusion.

Genetic: CAR-GPC3 T cells

Interventions

CAR-GPC3 T cells GENETIC

Self-controlled dose escalation will be applied to the first 3 - 6 subjects enrolled. Classical "3+3" dose escalation will be applied to subsequent subjects based on the self-controlled dose escalation study.

Also known as: GPC3 Redirected Autologous Cells

CAR-GPC3 T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18-70 years;
• Pathologically confirmed advanced hepatocellular carcinoma (HCC);
• ≥1 measurable target lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1);
• Tumor tissue positive for GPC3 expression per immunohistochemical staining (IHC) assay;
• Estimated survival \> 12 weeks;
• Child-Pugh grade A;
• ECOG performance score of 0-1;
• HBV-DNA \< 200 IU/mL if positive for HBsAg or HBcAb. Patients positive for HBsAg shall receive anti-viral treatment per "The guideline of prevention and treatment for chronic hepatitis B: a 2015 update";
• Have adequate venous access for apheresis or venous blood collection;
• White blood cells ≥ 2.5 x 109/L, platelet ≥ 60×109/L, haemoglobin ≥ 9.0 g/dL, lymphocyte ≥ 0.4×109/L
• Serum albumin ≥ 30 g/dL, serum lipase and amylase≤1.5 upper limit of normal (ULN), serum creatinine ≤ 1.5 ULN and endogenous creatinine clearance ≥ 40mL/min, ALT and AST ≤ 5 ULN, Serum total bilirubin ≤ 2.5 ULN, Prothrombin Time is less than 4s longer than normal;
• Negative serum pregnancy test within 14 days before CAR T infusion, and with willingness to use reliable contraceptive methods to avoid pregnancy until 12 months after CAR T infusions for females of childbearing age; Having undergone sterilization procedure or with willingness to use reliable contraceptive methods to avoid pregnancy for males with female partner of childbearing age during the study;
• Able to understand and sign the informed consent form

You may not qualify if:

• Pregnant or lactating female patients;
• Positive serum tests for HCV, HIV, or syphilis;
• Presence of HBV/HCV coinfection;
• Presence of any uncontrollable active infection, such as, but not limited to, active tuberculosis
• History of systemic administration of steroids (not including inhaled steroids), or other immunosuppressant drugs within 2 weeks before apheresis;
• History of allergy to immunotherapy and related drugs, or β-lactam antibiotics, or history of other severe allergy;
• History or current presence of hepatic encephalopathy;
• Presence of ascites with clinical significance that is defined as positive focused physical examination for ascites, or ascites that requires treatment intervention (not including any ascites shown on image examinations without the need for clinical intervention);
• ≥ 50% of normal liver occupied with HCC tumor tissue, or presence of tumor thrombus in the portal vein, or mesenteric vein, or inferior vena based on image analysis;
• Presence of HCC metastatic lesion in the central nervous system, or presence of other diseases of central nervous system with clinical significance;
• Presence of heart disease that requires treatment intervention, or poorly controlled hypertension (systolic pressure \> 160 mmHg, or diastolic pressure \> 100 mmHg);
• Presence of active auto-immune disease that requires immunosuppressant treatment;
• History of organ transplantation or currently on the waiting list for organ transplantation, including, but not limited to, liver transplantation;
• Anti-HCC therapies including, but not limited to, surgical resection, interventional therapy, radiation therapy, chemotherapy, and immunotherapy, within 2 weeks before apheresis;
• History of receiving anti-PD-1 or anti-PD-L1 monoclonal antibodies, or other immunotherapy;

Sponsors & Collaborators

• RenJi Hospital: lead
• CARsgen Therapeutics Co., Ltd.: collaborator

Study Sites (1)

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 20001, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Bo Zhai, MD

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2017
• First Posted: May 9, 2017
• Study Start: March 17, 2017
• Primary Completion: October 18, 2018
• Study Completion: October 18, 2018
• Last Updated: August 28, 2019

Record last verified: 2018-11

Locations

CN (1)