Clinical Trials /

CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions for CEA-Expressing Liver Metastases or Pancreas Cancer

NCT02850536

Description:

This is an open label, fixed dose, phase Ib trial of anti-CEA CAR-T cell infusions delivered via the hepatic artery or splenic vein using the Surefire Infusion System (SIS) for patients with CEA-expressing liver metastases or pancreas cancer.

Related Conditions:
  • Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions for CEA-Expressing Liver Metastases or Pancreas Cancer
  • Official Title: Phase Ib Trial of CAR-T Hepatic Artery Infusions or Pancreatic Venous Infusions Delivered With the Surefire Infusion System (SIS) for CEA-Expressing Liver Metastases or Pancreas Cancer

Clinical Trial IDs

  • ORG STUDY ID: 350-74
  • NCT ID: NCT02850536

Conditions

  • Liver Metastases

Interventions

DrugSynonymsArms
anti-CEA CAR-T cellsDesigner T cellsanti-CEA CAR-T cells

Purpose

This is an open label, fixed dose, phase Ib trial of anti-CEA CAR-T cell infusions delivered via the hepatic artery or splenic vein using the Surefire Infusion System (SIS) for patients with CEA-expressing liver metastases or pancreas cancer.

Detailed Description

      Patients undergo leukapheresis from which peripheral blood mononuclear cells are purified. T
      cells are activated and then re-engineered to express chimeric antigen receptors (CARs)
      specific for CEA. Cells are expanded in culture and returned to the patient by percutaneous
      hepatic artery infusion at specific cell doses. Prior to the first dose, each patient will
      undergo diagnostic angiography to verify suitable arterial anatomy. Three anti-CEA CAR-T
      doses per patient are planned at 1-week intervals. Low dose interleukin-2 will be given via
      an ambulatory infusion pump for 4 weeks. Normal liver and tumor biopsies will be obtained at
      the time of the initial diagnostic angiogram and during the final session following the 3rd
      CAR-T infusion.

      Patients with CEA+ liver metastases who exhibit in-liver control following CAR-T therapy who
      also have CEA+ primary pancreatic tumors may be eligible to receive direct intrapancreatic
      CAR-T retrograde venous infusions. A maximum of 2 infusions will be delivered. No additional
      IL-2 will be given and there will be no additional biopsies.
    

Trial Arms

NameTypeDescriptionInterventions
anti-CEA CAR-T cellsExperimentalThree infusions of gene-modified anti-CEA T cells over the course of 3 weeks into the hepatic artery via a percutaneous approach along with low dose IL-2.
  • anti-CEA CAR-T cells

Eligibility Criteria

        Inclusion Criteria:

          -  Patient with histologically confirmed diagnosis of CEA+ adenocarcinoma and liver
             metastases. Patient must have either histologic confirmation of the liver metastases
             or histologic documentation of the primary tumor and definitive radiologic evidence of
             liver involvement. Measurable disease is required with lesions of > 1.0 cm by CT.
             Soluble CEA is not acceptable as the sole measure of disease. Limited extrahepatic
             disease is acceptable if confined to the lungs or peritoneal cavity.

          -  Tumor must be CEA-expressing as demonstrated by elevated serum CEA levels (≥10ng/ml)
             or immunohistochemistry on a biopsy specimen. Archived tissue is acceptable for
             determination of CEA expression.

          -  Patient must be at least 18 years of age.

          -  Patient able to understand and sign informed consent.

          -  Patient with a life expectancy of greater than four months.

          -  Patient failed at least one line of standard systemic chemotherapy and has
             unresectable disease.

          -  Patient with performance status of 0 to 1 (ECOG).

          -  Patient with adequate organ function as defined in protocol.

          -  Acceptable hepatic vascular anatomy as determined by CT, MR, or conventional
             angiography. A nuclear medicine study will be performed to document the absence of a
             significant hepatic-pulmonary shunt (<20%).

        Exclusion Criteria:

          -  Female patients of childbearing age will be tested for pregnancy. Pregnant patients
             will be excluded from the study. Males who are actively seeking to have children will
             be made aware of the unknown risks of this study protocol on human sperm and the need
             to practice birth control.

          -  Patients with serious or unstable renal, hepatic, pulmonary, cardiovascular,
             endocrine, rheumatologic, or allergic disease based on history, physical exam and
             laboratory tests will be excluded, as outlined in section 5.2.8.

          -  Patients with active clinical disease caused by CMV, hepatitis B or C, HIV or
             tuberculosis will be excluded from the study.

          -  Patients who have had cytotoxic and/or radiation therapy within 4 weeks prior to entry
             into the trial or 4 weeks prior to infusion will be excluded. Patients with other
             concurrent malignancies will be excluded.

          -  Patients requiring systemic steroids will be excluded.

          -  Patients with unsuitable hepatic vascular anatomy will be excluded from the study.

          -  Patients with extrahepatic metastatic disease beyond the lungs or abdominal/
             retroperitoneal lymph nodes.

          -  Patients with >50% liver replacement at time of treatment will be excluded.

          -  Previous external beam radiotherapy to the liver.

          -  Portal vein thrombosis.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Safety of CAR-T cell hepatic artery infusions delivered using the Surefire Infusion System (SIS) as Measured by Number of Participants with Adverse Events
Time Frame:10 weeks
Safety Issue:
Description:To determine the safety and regimen limiting toxicity (RLT) of anti-CEA CAR-T hepatic artery infusions (HAI) via the Surefire Infusion System (SIS) for CEA-expressing liver metastases

Secondary Outcome Measures

Measure:Radiographic treatment response by MRI
Time Frame:10 weeks
Safety Issue:
Description:Changes in tumor size
Measure:Radiographic treatment response by PET
Time Frame:10 weeks
Safety Issue:
Description:Changes in tumor metabolic activity
Measure:CAR-T detection in liver tumors
Time Frame:10 weeks
Safety Issue:
Description:Quantification of CAR-T cells in liver tumor core biopsies
Measure:CAR-T detection in normal liver tissue
Time Frame:10 weeks
Safety Issue:
Description:Quantification of CAR-T cells in normal liver core biopsies
Measure:CAR-T detection in extrahepatic sites
Time Frame:10 weeks
Safety Issue:
Description:Quantification of CAR-T in blood samples
Measure:Serum Cytokine Levels
Time Frame:10 weeks
Safety Issue:
Description:Measurement of cytokines as indicators of immune response
Measure:CEA level
Time Frame:10 weeks
Safety Issue:
Description:Measurement of serum tumor marker (ng/ml)
Measure:Tumor biopsy
Time Frame:10 weeks
Safety Issue:
Description:Assessment of tumor necrosis and fibrosis
Measure:Safety of Direct Intrapancreatic CAR-T Retrograde Venous Infusions (RVI) Delivered Using the Surefire Infusion System (SIS)
Time Frame:10 weeks
Safety Issue:
Description:RVI via the Surefire Infusion System (SIS) for CEA+ Primary Pancreatic Tumors Following In-liver Disease Control

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Roger Williams Medical Center

Trial Keywords

  • Colorectal Cancer
  • Liver Metastases
  • Breast Cancer
  • Gastric Cancer
  • Pancreas Cancer
  • Carcinoembryonic antigen
  • CAR-T
  • Immunotherapy

Last Updated

October 30, 2020