Liver MetastasesPhase 1HITMNCT01373047
CEA-Expressing Liver Metastases Safety Study of Intrahepatic Infusions of Anti-CEA Designer T Cells
A Phase 1 study testing anti-CEA 2nd generation designer T cells in people with Liver Metastases, run by Roger Williams Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Metastases
- What is being tested?
- anti-CEA 2nd generation designer T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2011to Jul 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Able to understand and sign informed consent
- Life expectancy of greater than four months
- Good performance status (PS 0-1)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Roger Williams Medical Center
Providence, Rhode Island, 02908
About this study
Official title: 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.
Read the 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.
- Conditions
- Liver Metastases
- Being tested
- anti-CEA 2nd generation designer T cells
- Keywords
- liver metastases, immunotherapy, regional therapy, T cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-CEA 2nd generation designer T cellsBiological
Also called anti-CEA T cells, designer T cells
Three infusions of gene-modified T cells over the course of 6 weeks into the hepatic artery via a percutaneous approach.
| Study group | Role | What they receive |
|---|---|---|
| Intrahepatic anti-CEA designer T cells | Experimental | Not described Receives: Biological: anti-CEA 2nd generation designer T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 1 month
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roger Williams Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Steven C Katz, MD, Principal investigator, Roger Williams Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01373047
- Sponsor's protocol ID
- RWH 335-99
- Acronym
- HITM
- Status last verified
- Jul 2013
- First submitted
- 9 Jun 2011
- Last updated
- 30 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial Of Intrahepatic Infusion Of 2nd Generation Designer T Cells For Cea-Expressing Liver Metastases
- ClinicalTrials.gov ID
- NCT01373047
- Acronym / sponsor ID
- HITM / RWH 335-99
- Conditions
- Liver Metastases
- Keywords
- liver metastases, immunotherapy, regional therapy, T cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Roger Williams Medical CenterUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 14 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intrahepatic anti-CEA designer T cells | Experimental | Biological: anti-CEA 2nd generation designer T cells |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-CEA 2nd generation designer T cellsAlso: anti-CEA T cells, designer T cellsThree infusions of gene-modified T cells over the course of 6 weeks into the hepatic artery via a percutaneous approach. | Biological | Intrahepatic anti-CEA designer T cells |
Primary outcome
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
3 secondary outcomes
Tumor Response by CT or MRI and PET scan
Time frame: 1 month
Designer T cell distribution following infusion
Time frame: 1 month
Designer T cell survival and phenotype following infusion
Time frame: 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2013.
- Roger Williams Surgical OncologyLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven C Katz, MD principal investigator
Roger Williams Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing anti-CEA 2nd generation designer T cells in people with Liver Metastases, run by Roger Williams Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary 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). (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2013.