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

Phase 1
18 Years
Open (Enrolling)
Liver Metastases

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Trial Information

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

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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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).

Outcome Time Frame:

1 month

Safety Issue:


Principal Investigator

Steven C Katz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roger Williams Medical Center


United States: Food and Drug Administration

Study ID:

RWH 335-99



Start Date:

June 2011

Completion Date:

October 2013

Related Keywords:

  • Liver Metastases
  • liver metastases
  • immunotherapy
  • regional therapy
  • T cells
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Liver Neoplasms



Roger Williams Medical CenterProvidence, Rhode Island  02908-4735