CEA-Expressing Liver Metastases Safety Study of Intrahepatic Infusions of Anti-CEA Designer T Cells (HITM)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Roger Williams Medical Center
ClinicalTrials.gov Identifier:
NCT01373047
First received: June 9, 2011
Last updated: July 29, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to collect data on the safety and potential effectiveness of 2nd generation designer T cells delivered into the hepatic circulation in patients with liver metastases expressing the CEA tumor marker. Designer T cells are prepared by collecting white blood cells from the participant, and then modifying these cells in the laboratory so that they recognize the tumor antigen, CEA. These modified cells are then given back into the participant so that they can attack and kill tumor cells. The investigators hypothesize that regional delivery of the designer T cells directly into the hepatic artery will minimize systemic toxicity and optimize the changes for therapeutic effect.


Condition Intervention Phase
Liver Metastases
Biological: anti-CEA 2nd generation designer T cells
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial Of Intrahepatic Infusion Of 2nd Generation Designer T Cells For Cea-Expressing Liver Metastases

Resource links provided by NLM:


Further study details as provided by Roger Williams Medical Center:

Primary Outcome Measures:
  • Determine the safety of modified T cells delivered into the hepatic artery by documenting the type and severity of any side effects and establishing the Maximum Tolerated Dose (MTD). [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor Response by CT or MRI and PET scan [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    CT or MRI and PET imaging will be obtained before the first infusion and following the final infusion to document changes in liver tumor size and metabolic activity.

  • Designer T cell distribution following infusion [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Using liver tumor biopsy specimens and blood collection, we will determine the extent to which infused T cells enter the liver tumors in addition to circulation in the extrahepatic space.

  • Designer T cell survival and phenotype following infusion [ Time Frame: 1 month ] [ Designated as safety issue: No ]
    Using tissue obtained from biopsies in addition to blood samples, the duration of T cell persistence will be assessed, in addition to cell surface markers.


Enrollment: 8
Study Start Date: June 2011
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intrahepatic anti-CEA designer T cells Biological: anti-CEA 2nd generation designer T cells
Three infusions of gene-modified T cells over the course of 6 weeks into the hepatic artery via a percutaneous approach.
Other Names:
  • anti-CEA T cells
  • designer T cells

Detailed Description:

T cells have the power to destroy malignant cells under certain conditions, as demonstrated by the rare spontaneous remissions of cancer. However, the endogenous T cell response to cancer fails in the vast majority of patients and the tolerogenic conditions within the liver may pose additional immunologic barriers for those with intrahepatic metastases. The investigators modify patient T cells to kill malignant cells based on their expression of tumor antigens using antibody-defined recognition. The investigators will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors to yield "designer T cells" from normal patient cells. Prior studies in model systems demonstrated that recombinant IgCD28TCR could direct modified T cells to respond to antigen targets with IL2 secretion, cellular proliferation, and cytotoxicity - the hallmarks of an effective, self-sustaining immune response.

The present trial will test the regional infusion of anti-CEA designer T cells, given via the hepatic artery using a percutaneous approach. This is an intra-patient dose escalation trial, where patients will receive three doses over the course of six weeks. Doses are 10^8, 10^9 and 10^10 modified T cells. Patients are monitored for safety and response. Patients are on-study for one month after dosing.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed diagnosis of CEA+ adenocarcinoma and liver metastases
  • Liver metastases must be CEA-expressing as demonstrated by elevated serum CEA levels (≥10ng/ml) or immunohistochemistry on a biopsy specimen
  • Failure on at least one line of standard systemic chemotherapy and have unresectable liver disease
  • Measurable liver disease (> 1.0 cm by CT or MRI)
  • Extrahepatic disease is acceptable when limited to the lungs and/or abdominal lymph nodes
  • At least 18 years of age
  • Able to understand and sign informed consent
  • Life expectancy of greater than four months
  • Good performance status (PS 0-1)

Exclusion Criteria:

  • Pregnancy
  • Serious medical conditions including but not limited to liver, cardiopulmonary, and renal disease
  • Patients with a history of portal hypertension, cirrhosis, hepatitis, or with radiographic evidence of cirrhosis
  • Concurrent malignancy
  • Use of systemic steroids
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01373047

Locations
United States, Rhode Island
Roger Williams Medical Center
Providence, Rhode Island, United States, 02908
Sponsors and Collaborators
Roger Williams Medical Center
Investigators
Principal Investigator: Steven C Katz, MD Roger Williams Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Roger Williams Medical Center
ClinicalTrials.gov Identifier: NCT01373047     History of Changes
Other Study ID Numbers: RWH 335-99
Study First Received: June 9, 2011
Last Updated: July 29, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Roger Williams Medical Center:
liver metastases
immunotherapy
regional therapy
T cells

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

ClinicalTrials.gov processed this record on September 18, 2014