Colorectal CancerPhase 1/2TCR-CRC-001NCT03431311
T Cell Receptor Based Therapy of Metastatic Colorectal Cancer
A Phase 1/2 study testing Adoptive Cell Therapy (ACT) in people with Colorectal Cancer, run by Oslo University Hospital at 1 site in Norway.
Trial summary
T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Adoptive Cell Therapy (ACT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteNorway
- Study dates
- 8 Mar 2018to 12 Jun 2019
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with metastatic colon cancer which is MSI+ with the presence of the -1A deletion in TGFβRII gene, and positive for HLA-A02 genotype
- Measurable disease
- Female or male patients. Fertile females must have a negative pregnancy test before inclusion in the trial. Both fertile men and women must be ready and able to use highly effective methods of contraception, defined as use of oral, implanted, injectable, and mechanical or barrier products for the prevention of pregnancy during participation of the trial
- Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
- Age 18 years and older
- Life expectancy of at least 3 months
- Signed informed consent (by the subject or subject's legal representative) obtained before any trial-related procedures.
- Adequate organ function, measured by pre-defined laboratory values
Who cannot join
- Other metastatic malignancies
- Any other anti-tumour treatment within 4 weeks prior to first administration of cells.
- Steroid treatment, except substitution dose
- Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina or serious cardiac arrhythmia
- Active infection requiring antibiotic therapy
- Pregnancy or lactation
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- Known hypersensitivity to any of the components of the investigational product
- Patients who test positive for hepatitis B, C, HIV or syphilis
- Any reason why, in the opinion of the investigator, the patient should not participate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Protocol for Treatment Under Hospital Exemption: T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)
T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)
Read the detailed description
Patients with advanced metastatic colorectal cancer who have no other effective treatment options will be offered the treatment. These patients have a poor prognosis, and there is a strong need for improved therapy.
The patients will be given adoptive cell therapy (ACT) with Radium-1 TCR+ T cells transiently redirected against the TGFβRII frameshift antigen which is expressed in MSI+ colon cancer. The first report on TCR therapy in colon cancer was targeting carcinoembryonic antigen (CEA) where some evidence of clinical response was seen, but the T-cell function may have been inhibited due to the necessity to resolve the severe colitis which occurred due to the presence of CEA in normal cells in the colon. This demonstrates the feasibility of T-cell therapy in metastatic colon cancer, but also the limitations of targeting CEA as an antigen.
- Conditions
- Colorectal Cancer
- Being tested
- Adoptive Cell Therapy (ACT)
- Keywords
- MSI
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adoptive Cell Therapy (ACT)Biological
T cell receptor based therapy of metastatic colorectal cancer with mRNA-engineered T cells targeting mutant transforming growth factor beta receptor type II (TGFβII)
| Study group | Role | What they receive |
|---|---|---|
| Adoptive Cell Therapy (ACT) | Experimental | The ACT will be administered as two intravenous (i.v.) injections of GMP TCR T cells per week for 6 weeks.
Escalating dose per week, from 1 x108 cells (week 1) to 2x109 cells (week 4 onwards) using a central venous catheter. The doses listed indicate the maximum number of T cells per injection at any given time point. Receives: Biological: Adoptive Cell Therapy (ACT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
Measured: 2 years
Secondary outcomes (3)
Progression free survival (PFS)
PFS defined as time from treatment to objective progression (as assessed by RECIST v1.1)
Measured: 2 years
Radiological response rate (ORR)
ORR defined as the proportion of patients with an objective tumor response
Measured: 2 years
Overall survival (OS)
OS defined as time from treatment to date of death from any cause
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2018
- Study start8 Mar 2018
- Primary completion12 Jun 2019
- Study completion12 Jun 2019
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Svein Dueland, Oslo University Hospital
- Investigators
- Svein Dueland, MD PhD, Principal investigator, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03431311
- Sponsor's protocol ID
- TCR-CRC-001
- Acronym
- TCR-CRC-001
- Status last verified
- Jun 2019
- First submitted
- 30 Jan 2018
- Last updated
- 13 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Maggadottir SM, Dueland S, Mensali N, Hamre H, Andresen PA, Myhre MR, Juul HV, Bigalke I, Lundby M, Honnashagen TK, Saeboe-Larssen S, Josefsen D, Hagtvedt T, Walchli S, Kvalheim G, Inderberg EM. Transient TCR-based T cell therapy in a patient with advanced treatment-resistant MSI-high colorectal cancer. Mol Ther. 2024 Jun 5;32(6):2021-2029. doi: 10.1016/j.ymthe.2024.04.009. Epub 2024 Apr 6.
PubMed 38582964
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol for Treatment Under Hospital Exemption: T Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)
- ClinicalTrials.gov ID
- NCT03431311
- Acronym / sponsor ID
- TCR-CRC-001 / TCR-CRC-001
- Conditions
- Colorectal Cancer
- Keywords
- MSI
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Study start
- 8 Mar 2018 (actual)
- Primary completion
- 12 Jun 2019 (actual)
- Study completion
- 12 Jun 2019 (actual)
- First posted
- 13 Feb 2018 (actual)
- 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 Cell Receptor Based Therapy of Metastatic Colorectal Cancer With mRNA-engineered T Cells Targeting Transforming Growth Factor Beta Receptor Type II (TGFβII)
Detailed description
Patients with advanced metastatic colorectal cancer who have no other effective treatment options will be offered the treatment. These patients have a poor prognosis, and there is a strong need for improved therapy.
The patients will be given adoptive cell therapy (ACT) with Radium-1 TCR+ T cells transiently redirected against the TGFβRII frameshift antigen which is expressed in MSI+ colon cancer. The first report on TCR therapy in colon cancer was targeting carcinoembryonic antigen (CEA) where some evidence of clinical response was seen, but the T-cell function may have been inhibited due to the necessity to resolve the severe colitis which occurred due to the presence of CEA in normal cells in the colon. This demonstrates the feasibility of T-cell therapy in metastatic colon cancer, but also the limitations of targeting CEA as an antigen.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adoptive Cell Therapy (ACT) | Experimental | Biological: Adoptive Cell Therapy (ACT)The ACT will be administered as two intravenous (i.v.) injections of GMP TCR T cells per week for 6 weeks. Escalating dose per week, from 1 x108 cells (week 1) to 2x109 cells (week 4 onwards) using a central venous catheter. The doses listed indicate the maximum number of T cells per injection at any given time point. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with metastatic colon cancer which is MSI+ with the presence of the -1A deletion in TGFβRII gene, and positive for HLA-A02 genotype
- Measurable disease
- Female or male patients. Fertile females must have a negative pregnancy test before inclusion in the trial. Both fertile men and women must be ready and able to use highly effective methods of contraception, defined as use of oral, implanted, injectable, and mechanical or barrier products for the prevention of pregnancy during participation of the trial
- Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1
- Age 18 years and older
Key exclusion criteria (9 listed)
- Other metastatic malignancies
- Any other anti-tumour treatment within 4 weeks prior to first administration of cells.
- Steroid treatment, except substitution dose
- Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina or serious cardiac arrhythmia
- Active infection requiring antibiotic therapy
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 |
|---|---|---|
| Adoptive Cell Therapy (ACT)T cell receptor based therapy of metastatic colorectal cancer with mRNA-engineered T cells targeting mutant transforming growth factor beta receptor type II (TGFβII) | Biological | Adoptive Cell Therapy (ACT) |
Primary outcome
Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
Time frame: 2 years
Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0
3 secondary outcomes
Progression free survival (PFS)
Time frame: 2 years
Radiological response rate (ORR)
Time frame: 2 years
Overall survival (OS)
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2019.
- Derived from this study: PubMed 38582964Maggadottir SM, Dueland S, Mensali N, Hamre H, Andresen PA, Myhre MR, Juul HV, Bigalke I, Lundby M, Honnashagen TK, Saeboe-Larssen S, Josefsen D, Hagtvedt T, Walchli S, Kvalheim G, Inderberg EM. Transient TCR-based T cell therapy in a patient with advanced treatment-resistant MSI-high colorectal cancer. Mol Ther. 2024 Jun 5;32(6):2021-2029. doi: 10.1016/j.ymthe.2024.04.009. Epub 2024 Apr 6.
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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.
Svein Dueland, MD PhD principal investigator
Oslo University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Adoptive Cell Therapy (ACT) in people with Colorectal Cancer, run by Oslo University Hospital at 1 site in Norway.
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 8 inclusion and 9 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: stopped early, as of the sponsor's last update on 13 Jun 2019. 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 Norway. 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 combined 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.
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?
The study was stopped early (reason given: Sponsor decision). 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?
Incidence, nature, and severity of adverse events graded according to NCI CTCAE v4.0 (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03431311, which also lists 1 linked publication.
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 13 Jun 2019.