Metastatic CancersPhase 2NCT01723306
Phase II/Pilot Study of 2nd Generation Anti-CEA Designer T Cells in Adenocarcinomas
A Phase 2 study testing Gene Modified T Cells in people with Metastatic Cancers, run by Roger Williams Medical Center at 1 site in United States.
Trial summary
T cells can penetrate virtually every biologic space and have the power to dispose of normal or malignant cells as seen in viral and autoimmune diseases and in the rare spontaneous remis-sions of cancer. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Metastatic Cancers
- What is being tested?
- Gene Modified T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Aug 2017
- Phase
- Phase 2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically confirmed diagnosis of CEA-expressing adenocarcinoma. Patient may have measurable tumor by physical examination or by radiologic studies, and/or evaluable disease, including bone lesions. Soluble CEA is not acceptable as the sole measure of disease, although it may be followed in addition to measurable or other evaluable disease.
- Tumor must be CEA-expressing as demonstrated by elevated serum CEA levels(>10 ng/ml). Preference will be given to patients with CEA >100 ng/mL to increase the sensitivity of CEA as a measure of the tumor response.
- Where preserved tumor tissue is available, direct immuno¬histochemical staining of tumor is obtained to demonstrate CEA expression on tumor cells.
- Patient must be at least 18 years of age.
- Patient able to understand and sign informed consent.
- Patient with a life expectancy of greater than four months.
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- Patient failed standard potentially curative therapy.
- Patient with performance status of 0 to 1 (ECOG).
- Patient with adequate organ function as defined by:
- ANC 1.0, platelets 50,000, Hgb 8.0; patient may be transfused to achieve Hgb 8.0 to satisfy enrollment criteria, or as otherwise indicated by symptoms for Hgb >8.0.
- Creatinine 1.5mg/dl or creatinine clearance 60cc/min.
- Direct bilirubin 1.5 mg/dl.
- No evidence of congestive heart failure, symptoms of coronary artery disease, serious cardiac arrhythmias, including atrial fibrillation/atrial flutter, evidence of prior myocardial infarction by history or by EKG.
- A normal cardiac stress test for inducible ischemia or arrhythmia within 12 weeks prior to enrollment for all patients over 50 years old or those with abnormal EKG or any history or symptoms suggestive of cardiac disease.
- -- No serious, symptomatic obstructive or emphysematous lung disease, or asthma requiring intravenous medications within the past 12 months; no serious lung disease associated with dyspnea at normal activity levels grade III) or at rest (grade IV), due to any cause (including cancer metastases and pleural effusions). The patient will be ineligible if PFTs show an FEV1 <1.3 liters or a DLCO <50% within 12 weeks of study entry.
Who cannot join
- Female patients of childbearing age will be tested for pregnancy; pregnant patients will be excluded from the study. Males who are actively seeking to have children will be made aware of the unknown risks of this study protocol of human sperm and the need to practice birth control.
- Patients with serious or unstable renal, hepatic, pulmonary, cardio¬vascular, endocrine, rheumatologic, or allergic disease based on history, physical exam and laboratory tests will be excluded, as outlined in section 5.2.8.
- Patients with active clinical disease caused by CMV, hepatitis B or C, HIV or tuberculosis will be excluded from the study.
- Patients who have had cytotoxic and/or radiation therapy in the four weeks prior to entry into the trial will be excluded.
- Patients with other concurrent malignancies will be excluded.
- Patients requiring systemic steroids will be excluded.
- Patients previously treated with investigational agents will be excluded
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 II/Pilot Study of 2nd Generation Anti-CEA Esigner T Cells in Adenocarcinomas"
T cells can penetrate virtually every biologic space and have the power to dispose of normal or malignant cells as seen in viral and autoimmune diseases and in the rare spontaneous remis-sions of cancer. However, T cells are easily tolerized to self or tumor antigens and "immune surveillance" has manifestly failed in every cancer that is clinically apparent. It is the goal of these studies to supply the specificities and affinities to patient T cells without regard for their "endogenous" T cell receptor repertoire, directed by antibody-defined recognition to kill malignant cells based on their expression of antigen. We will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors to yield "designer T cells" from normal patient cells. This extends the approach of Anderson, Rosenberg and co-workers to introduce or augment expression of genes in patients' T cells in a therapeutic setting.
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. It therefore becomes of paramount interest to extend these studies to a human system of widespread clinical relevance to explore the clinical potential of this new technology. The target antigen for these studies is carcinoembryonic antigen (CEA) which is predominantly expressed on tumors of the colon and rectum, breast, pancreas and other sites.
Read the detailed description
CEA is perhaps the most prominent tumor marker among malignancies of epithelial origin: colorectal carcinoma, with 60-94% of tumors positive in patients with advanced disease; breast carcinoma, with 30-60% of metastatic cases positive for CEA; and cancers of the lung, liver, pancreas, head and neck, bladder, cervix and prostate with 30% or more with CEA+ tumors.
The application of these therapies in the four Phase II/Pilot clinical sub studies listed below proceed after collecting patient lymphocytes by leukapheresis, which are then modified by transfer of the chimeric gene for Ig-CD28-TCRzeta. Cells are selected in culture with amplification and activation of the now-specific anti-tumor T cells. These are then re infused into the patients, with IL2 supplementation, and toxicity and response are monitored.
There are four sub studies embedded within this Phase II Study of Second Generation Designer T Cells in CEA-expressing Adenocarcinomas. The embedded studies are:
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Gastric Cancers (CEA-G)
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Colorectal Cancers (CEA-C)
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Lung Cancers (CEA-L)
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Solid Tumors (CEA-S)
A total of 12 subjects per protocol or a total of 48 subjects will be enrolled combining the enrollment of the 4 CEA-expressing protocols.
- Conditions
- Metastatic Cancers
- Being tested
- Gene Modified T Cells
- Keywords
- T cells, gene transfer, immunotherapy, metastatic cancers, lung cancer, gastric cancer, colorectal cancer, solid tumors
- Medical subject headings
- Neoplasms, Lung Neoplasms, Stomach Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gene Modified T CellsGenetic
Also called 2nd Generation Designer T Cells
Subjects will undergo T cell leukopheresis. The collected T cells will be genetically modified, and then re-infused peripherally. IL2 will be given concomitantly for 30 days post modified T cell infusion via CADD pump.
| Study group | Role | What they receive |
|---|---|---|
| 2nd Generation Designer T Cells | Experimental | All participants will receive gene modified T cells, with concomitant IL2 for 30 days post infusion. Receives: Genetic: Gene Modified T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy
Monitoring of CEA levels, pre and post infusion of T cells. Monitoring of CT and PET scans pre and post infusion.
Measured: 24 months
Secondary outcomes (1)
Safety
Monitoring and recording of all adverse and serious adverse events using CTC 4.0 criteria.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2012 (estimated)
- Study startOct 2012
- Primary completionOct 2016 (estimated)
- Study completionAug 2017 (estimated)
Why it stopped: Funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic CancersStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Roger Williams Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Richard Junghans, PhD, MD, Roger Williams Medical Center
- Investigators
- Richard P Junghans, PhD, MD, Principal investigator, Roger Williams Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01723306
- Sponsor's protocol ID
- 306-04
- Status last verified
- Jun 2016
- First submitted
- 1 Nov 2012
- Last updated
- 14 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "Phase II/Pilot Study of 2nd Generation Anti-CEA Esigner T Cells in Adenocarcinomas"
- ClinicalTrials.gov ID
- NCT01723306
- Acronym / sponsor ID
- 306-04
- Conditions
- Metastatic Cancers
- Keywords
- T cells, gene transfer, immunotherapy, metastatic cancers, lung cancer, gastric cancer, colorectal cancer, solid tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Funding
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Roger Williams Medical CenterUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Oct 2016 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 7 Nov 2012 (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.
T cells can penetrate virtually every biologic space and have the power to dispose of normal or malignant cells as seen in viral and autoimmune diseases and in the rare spontaneous remis-sions of cancer. However, T cells are easily tolerized to self or tumor antigens and "immune surveillance" has manifestly failed in every cancer that is clinically apparent. It is the goal of these studies to supply the specificities and affinities to patient T cells without regard for their "endogenous" T cell receptor repertoire, directed by antibody-defined recognition to kill malignant cells based on their expression of antigen. We will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors to yield "designer T cells" from normal patient cells. This extends the approach of Anderson, Rosenberg and co-workers to introduce or augment expression of genes in patients' T cells in a therapeutic setting.
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. It therefore becomes of paramount interest to extend these studies to a human system of widespread clinical relevance to explore the clinical potential of this new technology. The target antigen for these studies is carcinoembryonic antigen (CEA) which is predominantly expressed on tumors of the colon and rectum, breast, pancreas and other sites.
Detailed description
CEA is perhaps the most prominent tumor marker among malignancies of epithelial origin: colorectal carcinoma, with 60-94% of tumors positive in patients with advanced disease; breast carcinoma, with 30-60% of metastatic cases positive for CEA; and cancers of the lung, liver, pancreas, head and neck, bladder, cervix and prostate with 30% or more with CEA+ tumors.
The application of these therapies in the four Phase II/Pilot clinical sub studies listed below proceed after collecting patient lymphocytes by leukapheresis, which are then modified by transfer of the chimeric gene for Ig-CD28-TCRzeta. Cells are selected in culture with amplification and activation of the now-specific anti-tumor T cells. These are then re infused into the patients, with IL2 supplementation, and toxicity and response are monitored.
There are four sub studies embedded within this Phase II Study of Second Generation Designer T Cells in CEA-expressing Adenocarcinomas. The embedded studies are:
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Gastric Cancers (CEA-G)
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Colorectal Cancers (CEA-C)
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Lung Cancers (CEA-L)
- A Phase II Pilot Study of Second Generation Anti CEA Designer T Cells in Solid Tumors (CEA-S)
A total of 12 subjects per protocol or a total of 48 subjects will be enrolled combining the enrollment of the 4 CEA-expressing protocols.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 2nd Generation Designer T Cells | Experimental | Genetic: Gene Modified T CellsAll participants will receive gene modified T cells, with concomitant IL2 for 30 days post infusion. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Patients with histologically confirmed diagnosis of CEA-expressing adenocarcinoma. Patient may have measurable tumor by physical examination or by radiologic studies, and/or evaluable disease, including bone lesions. Soluble CEA is not acceptable as the sole measure of disease, although it may be followed in addition to measurable or other evaluable disease.
- Tumor must be CEA-expressing as demonstrated by elevated serum CEA levels(>10 ng/ml). Preference will be given to patients with CEA >100 ng/mL to increase the sensitivity of CEA as a measure of the tumor response.
- Where preserved tumor tissue is available, direct immuno¬histochemical staining of tumor is obtained to demonstrate CEA expression on tumor cells.
- Patient must be at least 18 years of age.
- Patient able to understand and sign informed consent.
Key exclusion criteria (7 listed)
- Female patients of childbearing age will be tested for pregnancy; pregnant patients will be excluded from the study. Males who are actively seeking to have children will be made aware of the unknown risks of this study protocol of human sperm and the need to practice birth control.
- Patients with serious or unstable renal, hepatic, pulmonary, cardio¬vascular, endocrine, rheumatologic, or allergic disease based on history, physical exam and laboratory tests will be excluded, as outlined in section 5.2.8.
- Patients with active clinical disease caused by CMV, hepatitis B or C, HIV or tuberculosis will be excluded from the study.
- Patients who have had cytotoxic and/or radiation therapy in the four weeks prior to entry into the trial will be excluded.
- Patients with other concurrent malignancies will be excluded.
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 |
|---|---|---|
| Gene Modified T CellsAlso: 2nd Generation Designer T CellsSubjects will undergo T cell leukopheresis. The collected T cells will be genetically modified, and then re-infused peripherally. IL2 will be given concomitantly for 30 days post modified T cell infusion via CADD pump. | Genetic | 2nd Generation Designer T Cells |
Primary outcome
Efficacy
Time frame: 24 months
Monitoring of CEA levels, pre and post infusion of T cells. Monitoring of CT and PET scans pre and post infusion.
1 secondary outcome
Safety
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2016.
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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.
Richard P Junghans, PhD, 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 2 study testing Gene Modified T Cells in people with Metastatic Cancers, 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 15 inclusion and 7 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: paused, as of the sponsor's last update on 14 Jun 2016. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Efficacy (time frame: 24 months). 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 14 Jun 2016.