Breast CancerPhase 1NCT00673829
Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer
A Phase 1 study testing Gene Modified T Cells and Gene Modified T Cells and Interleukin 2 in people with Breast Cancer, run by Roger Williams Medical Center at 2 sites in United States.
Trial summary
The purpose of this study is to collect data on the safety and effectiveness of 2nd generation designer T cells in patients with breast cancer. 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Gene Modified T Cells and Gene Modified T Cells and Interleukin 2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2008to Dec 2018
- 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
- Must have cancer of the breast
- Must have metastatic or unresectable locally advanced disease
- Tumor must express CEA by tumor staining or by elevated serum CEA (>10 ng/ml)
- Must have measurable disease radiologically or by physical exam
- Must have failed potentially curative standard therapy
- Must be 18 years of age or older
- Good performance status (PS 0-1)
Who cannot join
- Requiring systemic steroids
- Serious medical conditions
- Concurrent malignancies
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Tufts University Medical Center
Boston, Massachusetts, 02115
Roger Williams Medical Center
Providence, Rhode Island, 02908
About this study
Official title: Phase Ia/Ib Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer
The purpose of this study is to collect data on the safety and effectiveness of 2nd generation designer T cells in patients with breast cancer. 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 to the participant so that they can attack and kill tumor cells.
Read the detailed description
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 remissions 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 this study 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. 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 prominently expressed on tumors of the stomach, colon and rectum, breast, pancreas and other sites.
For the Phase Ia component, patients receive a single dose of gene-modified autologous T cells on this dose-escalation trial. Doses are 10^9 and 10^10 modified T cells. Patients are monitored for safety and response. Patients are on-study for one month after dosing.
For the Phase Ib component, patients receive a fixed dose of gene-modified T cells (10^11 cells), randomized to receive T cell growth factor interleukin 2 (+IL2) [Experimental] or not (-IL2) [Control]. The IL2 is administered outpatient by continuous infusion for a two-week period. On Day +2 and Day +10, the patient's tumor is biopsied to assess the designer T cell presence in the tumor as a means of judging the benefit of added IL2. Patients will also be followed for tumor response.
- Conditions
- Breast Cancer
- Being tested
- Gene Modified T Cells, Gene Modified T Cells and Interleukin 2
- Keywords
- Breast Cancer, T cells, Gene Transfer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gene Modified T CellsBiological
Also called Designer T-Cells, CEA
Gene Modified T Cells Phase Ia: One time infusion Modified TCells given through a vein in the arm or a catheter over a 30-60 minute period
Gene Modified T Cells and Interleukin 2Biological
Also called Designer T-Cells, CEA
One time infusion Modified T Cells without or with (randomized) continuous infusion outpatient interleukin 2 (IL2) for two weeks
| Study group | Role | What they receive |
|---|---|---|
| Phase Ia | Experimental | Not described Receives: Biological: Gene Modified T Cells |
| Phase Ib: Control | Experimental | Not described Receives: Biological: Gene Modified T Cells and Interleukin 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ia:Determine the safety of using modified T-cells by documenting the type and severity of any side effects and establishing the maximum tolerated dose (MTD).
Measured: 1 Month
Phase Ib: Determine optimal biologic dose (OBD) in terms of value of added interleukin 2.
Measured: 1 Month
Secondary outcomes (3)
Tumor Response
Measured: 1 Month
Pharmacokinetic
Measured: 1 month
Pharmacodynamic
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 posted7 May 2008 (estimated)
- Study startMay 2008
- Primary completionDec 2017 (estimated)
- Study completionDec 2018 (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 Breast CancerStudies 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
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Roger Williams Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Richard P Junghans, PhD, MD, Principal investigator, Roger Williams Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00673829
- Sponsor's protocol ID
- 300-04
- Status last verified
- Jun 2016
- First submitted
- 5 May 2008
- Last updated
- 17 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ia/Ib Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00673829
- Acronym / sponsor ID
- 300-04
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, T cells, Gene Transfer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Funding
- Enrolment
- 26 participants (estimated)
- Lead sponsor
- Roger Williams Medical CenterUniversity, hospital or other
- Study start
- May 2008
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 7 May 2008 (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 effectiveness of 2nd generation designer T cells in patients with breast cancer. 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 to the participant so that they can attack and kill tumor cells.
Detailed description
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 remissions 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 this study 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. 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 prominently expressed on tumors of the stomach, colon and rectum, breast, pancreas and other sites.
For the Phase Ia component, patients receive a single dose of gene-modified autologous T cells on this dose-escalation trial. Doses are 10^9 and 10^10 modified T cells. Patients are monitored for safety and response. Patients are on-study for one month after dosing.
For the Phase Ib component, patients receive a fixed dose of gene-modified T cells (10^11 cells), randomized to receive T cell growth factor interleukin 2 (+IL2) [Experimental] or not (-IL2) [Control]. The IL2 is administered outpatient by continuous infusion for a two-week period. On Day +2 and Day +10, the patient's tumor is biopsied to assess the designer T cell presence in the tumor as a means of judging the benefit of added IL2. Patients will also be followed for tumor response.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase Ia | Experimental | Biological: Gene Modified T Cells |
| Phase Ib: Control | Experimental | Biological: Gene Modified T Cells and Interleukin 2 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Must have cancer of the breast
- Must have metastatic or unresectable locally advanced disease
- Tumor must express CEA by tumor staining or by elevated serum CEA (>10 ng/ml)
- Must have measurable disease radiologically or by physical exam
- Must have failed potentially curative standard therapy
Key exclusion criteria (3 listed)
- Requiring systemic steroids
- Serious medical conditions
- Concurrent malignancies
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: Designer T-Cells, CEAGene Modified T Cells Phase Ia: One time infusion Modified TCells given through a vein in the arm or a catheter over a 30-60 minute period | Biological | Phase Ia |
| Gene Modified T Cells and Interleukin 2Also: Designer T-Cells, CEAOne time infusion Modified T Cells without or with (randomized) continuous infusion outpatient interleukin 2 (IL2) for two weeks | Biological | Phase Ib: Control |
Primary outcome
Phase Ia:Determine the safety of using modified T-cells by documenting the type and severity of any side effects and establishing the maximum tolerated dose (MTD).
Time frame: 1 Month
Phase Ib: Determine optimal biologic dose (OBD) in terms of value of added interleukin 2.
Time frame: 1 Month
3 secondary outcomes
Tumor Response
Time frame: 1 Month
Pharmacokinetic
Time frame: 1 month
Pharmacodynamic
Time frame: 1 Month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 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
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gene Modified T Cells and Gene Modified T Cells and Interleukin 2 in people with Breast Cancer, run by Roger Williams Medical Center at 2 sites 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 7 inclusion and 3 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 17 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 2 sites 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?
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?
Phase Ia:Determine the safety of using modified T-cells by documenting the type and severity of any side effects and establishing the maximum tolerated dose (MTD). (time frame: 1 Month). The study lists 2 primary outcomes in all. 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 17 Jun 2016.