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CAR-T Hepatic Artery Infusions for CEA-Expressing Liver Metastases (HITM-SURE)

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ClinicalTrials.gov Identifier: NCT02850536
Recruitment Status : Recruiting
First Posted : August 1, 2016
Last Update Posted : February 3, 2017
University of Colorado, Denver
Information provided by (Responsible Party):
Roger Williams Medical Center

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

Condition or disease Intervention/treatment Phase
Liver Metastases Biological: anti-CEA CAR-T cells Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Trial of CAR-T Hepatic Artery Infusions Delivered With the Surefire Infusion System (SIS) for CEA-Expressing Liver Metastases
Actual Study Start Date : February 1, 2017
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: anti-CEA CAR-T cells
Three 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.
Biological: anti-CEA CAR-T cells
Gene modified patient T cells
Other Name: Designer T cells

Primary Outcome Measures :
  1. 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 ]
    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 :
  1. Radiographic treatment response by MRI [ Time Frame: 10 weeks ]
    Changes in tumor size

  2. Radiographic treatment response by PET [ Time Frame: 10 weeks ]
    Changes in tumor metabolic activity

  3. CAR-T detection in liver tumors [ Time Frame: 10 weeks ]
    Quantification of CAR-T cells in liver tumor core biopsies

  4. CAR-T detection in normal liver tissue [ Time Frame: 10 weeks ]
    Quantification of CAR-T cells in normal liver core biopsies

  5. CAR-T detection in extrahepatic sites [ Time Frame: 10 weeks ]
    Quantification of CAR-T in blood samples

  6. Serum Cytokine Levels [ Time Frame: 10 weeks ]
    Measurement of cytokines as indicators of immune response

  7. CEA level [ Time Frame: 10 weeks ]
    Measurement of serum tumor marker (ng/ml)

  8. Tumor biopsy [ Time Frame: 10 weeks ]
    Assessment of tumor necrosis and fibrosis

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02850536

Contact: Ashley Moody, RN 401-456-2268 ext 2268 ALarkin@chartercare.org
Contact: Tracey MacDermott 303-724-2757 Tracey.MacDermott@ucdenver.edu

United States, Colorado
University of Colorado Hospital Recruiting
Aurora, Colorado, United States, 80045
Contact: Tracey MacDermott    303-724-2757    Tracey.MacDermott@ucdenver.edu   
Principal Investigator: Richard Schulick, MD         
United States, Rhode Island
Roger Williams Medical Center Recruiting
Providence, Rhode Island, United States, 02908
Contact: Ashley Moody, RN    401-456-2268 ext 2268    ALarkin@chartercare.org   
Principal Investigator: Steven C. Katz, MD         
Sponsors and Collaborators
Roger Williams Medical Center
University of Colorado, Denver
Principal Investigator: Steven C. Katz, MD Roger Williams Medical Center
Principal Investigator: Richard Schulick, MD University of Colorado, Denver

Responsible Party: Roger Williams Medical Center
ClinicalTrials.gov Identifier: NCT02850536     History of Changes
Other Study ID Numbers: 350-74
First Posted: August 1, 2016    Key Record Dates
Last Update Posted: February 3, 2017
Last Verified: February 2017

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

Keywords provided by Roger Williams Medical Center:
Colorectal Cancer
Liver Metastases
Breast Cancer
Gastric Cancer
Pancreas Cancer
Carcinoembryonic antigen

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Liver Neoplasms
Neoplastic Processes
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases