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

Phase I Trial Of Intrahepatic Infusion Of 2nd Generation Designer T Cells For Cea-Expressing Liver Metastases

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.

Study Overview

• Status: Completed
• Conditions: Liver Metastases
• Intervention / Treatment: Biological: anti-CEA 2nd generation 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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02908
      • Roger Williams Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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).	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response by CT or MRI and PET scan	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.	1 month
Designer T cell distribution following infusion	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.	1 month
Designer T cell survival and phenotype following infusion	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.	1 month

Collaborators and Investigators

• Sponsor: Roger Williams Medical Center
• Investigators: Principal Investigator: Steven C Katz, MD, Roger Williams Medical Center

Publications and helpful links

Helpful Links

• Roger Williams Surgical Oncology

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: June 9, 2011
• First Submitted That Met QC Criteria: June 13, 2011
• First Posted (Estimate): June 14, 2011

Study Record Updates

• Last Update Posted (Estimate): July 30, 2013
• Last Update Submitted That Met QC Criteria: July 29, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: immunotherapy; liver metastases; T cells; regional therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: RWH 335-99