View Clinical Trial (Medical Research Study)
Phase I Trial Of Intrahepatic Infusion Of 2nd Generation Designer T Cells For Cea-Expressing Liver Metastases
| City: |
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Providence |
| State: |
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Rhode Island |
| Zip Code: |
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02908 |
| Conditions: |
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Liver Metastases |
| Purpose: |
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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.
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| Study Summary: |
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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.
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| Criteria: |
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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
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| NCT ID: |
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NCT01373047 |
| Primary Contact: |
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Principal Investigator
Steven C Katz, MD
Roger Williams Medical Center
Robin A Davies, BA, BSN, RN
Phone: 401-456-2419
Email: rdavies@chartercare.org
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| Backup Contact: |
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N/A |
| Location Contact: |
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Providence, Rhode Island 02908
United States
Robin A Davies, BA, BSN, RN
Email: rdavies@chartercare.org
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 20, 2013 |
| Modifications to this listing: |
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