Clinical trial NCT01373047: CEA-Expressing Liver Metastases Safety Study of Intrahepatic Infusions of Anti-CEA Designer T Cells
Official title: Phase I Trial Of Intrahepatic Infusion Of 2nd Generation Designer T Cells For Cea-Expressing Liver Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Liver Metastases
Keywords: liver metastases
immunotherapy
regional therapy
T cells
Lead sponsor: Roger Williams Medical Center
Sponsor class: OTHER
First posted: 2011-06-14
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
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).
timeFrame: 1 month
Secondary outcomes:
measure: Tumor Response by CT or MRI and PET scan
timeFrame: 1 month
measure: Designer T cell distribution following infusion
timeFrame: 1 month
measure: Designer T cell survival and phenotype following infusion
timeFrame: 1 month
Other outcomes:
Locations:
city: Providence
country: United States
facility: Roger Williams Medical Center
state: Rhode Island
Study officials:
affiliation: Roger Williams Medical Center
name: Steven C Katz, MD
role: PRINCIPAL_INVESTIGATOR
References: