ColoRectal CancerHLA-E CCRNCT02980146
Impact of HLA-E Overexpression by Tumor Cells on the Biology of TIL in Colorectal Cancer
An observational study of ColoRectal Cancer, run by Nantes University Hospital at 1 site in France.
Trial summary
Accumulating evidences suggest that colorectal cancer (CRC) progression is not solely determined by the genetic abnormalities of the tumor cells but also by the host response. Indeed, recent studies in CRC have associated improved survival with a high number of tumor-infiltrating (TIL) memory and cytotoxic T… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- ColoRectal Cancer
- What is being tested?
- Non interventional study
- How many people
- 28 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jun 2016to 26 Jun 2017
- Phase
- Observational
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Major patients treated surgically for colorectal cancer at the Nantes University Hospital or the West Institute of Cancerology
Who may be able to join
- Major patients treated surgically for colorectal cancer at the Nantes University Hospital or the West Institute of Cancerology
- Patients agreeing to participate in the study
- Non inclusion Criteria:
- Age> 85 years
- Neoadjuvant or immunosuppressive therapy for other pathology
- Size of the tumor insufficient to carry out all the samples dedicated to the research without constraining the diagnostic step (tumoral sampling at least equal to 1 cm3)
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Correlation Between HLA-E Overexpression by Tumor Cells and the Biology of Tumor-infiltrating Lymphocytes Depending on the Microsatellite Status in Colorectal Cancer.
Accumulating evidences suggest that colorectal cancer (CRC) progression is not solely determined by the genetic abnormalities of the tumor cells but also by the host response. Indeed, recent studies in CRC have associated improved survival with a high number of tumor-infiltrating (TIL) memory and cytotoxic T lymphocytes, suggesting a link between tumor progression and in situ T cell response. Gene expression profiling studies have clearly isolated a well-known subgroup of CRC characterized by microsatellite instability (MSI) CRC, associated with a strong immune response signature involving both Th1/cytotoxic and immune evasion pathways. Moreover, the investigators have previously shown that HLA-E/β2m is overexpressed by tumor cells in roughly 20% of CRC and is associated with a worse prognosis, most likely due to NK and T effector cell functions upon engagement with the inhibitory NK receptor CD94/NKG2A. However, our recent results on an enlarger cohort of patients suggest that if this observation holds true for MSS CRC, HLA-E over-expression is inversely associated with a good prognosis in MSI CRC. Thus, the phenotype and function of TIL, depending on the MSI/MSS status of CRC have to be precised. The investigators hypothesized that in MSI CRC, known to express a high number of MSI-H related frameshift peptides which represent a pool of tumor specific antigens, HLA-E could present peptides to TCR of non conventional CD8+ HLA-E-restricted alpha-betaT cells (also expressing CD94), then inducing a strong antitumor cytolytic activity. Therefore, the aim of this project is to determine the exact phenotype, function and specificity of the CD94+ TIL in CRC, depending on both the HLA-E and the MSI/MSS status of tumor cells. These results could impact the clinical practice as anti-NKG2A monoclonal antibodies or frameshift peptide based immunotherapy that could be promising new therapeutic options in CRC patients.
- Conditions
- ColoRectal Cancer
- Being tested
- Non interventional study
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non interventional studyOther
| Study group | Role | What they receive |
|---|---|---|
| Group "patients with colorectal cancer" | Major patients treated surgically for colorectal cancer at Nantes University Hospital or at the Institut de Cancerologie de l'Ouest and agreeing to participate in the study Receives: Other: Non interventional study |
What is being measured
The primary outcome is the main question the study is designed to answer.
The phenotype of TIL will be precised by immunohistochemisry and flow cytometry using various combinations of monoclonal antibodies to identify different subset of TIL and their frequency, especially those expressing NKG2A or NKG2C chain.
Measured: Until 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2016 (estimated)
- Study start1 Jun 2016
- Primary completion26 Jun 2017
- Study completion26 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ColoRectal CancerStudies of the same condition, open and under way.
- More trials run by Nantes 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- U892 INSERM Team 3
- Responsible party
- Sponsor
- Investigators
- Céline BOSSARD, Pr, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02980146
- Sponsor's protocol ID
- RC16_0212
- Acronym
- HLA-E CCR
- Status last verified
- Apr 2019
- First submitted
- 21 Nov 2016
- Last updated
- 18 Apr 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Correlation Between HLA-E Overexpression by Tumor Cells and the Biology of Tumor-infiltrating Lymphocytes Depending on the Microsatellite Status in Colorectal Cancer.
- ClinicalTrials.gov ID
- NCT02980146
- Acronym / sponsor ID
- HLA-E CCR / RC16_0212
- Conditions
- ColoRectal Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- U892 INSERM Team 3
- Study start
- 1 Jun 2016
- Primary completion
- 26 Jun 2017 (actual)
- Study completion
- 26 Jun 2017 (actual)
- First posted
- 2 Dec 2016 (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.
Accumulating evidences suggest that colorectal cancer (CRC) progression is not solely determined by the genetic abnormalities of the tumor cells but also by the host response. Indeed, recent studies in CRC have associated improved survival with a high number of tumor-infiltrating (TIL) memory and cytotoxic T lymphocytes, suggesting a link between tumor progression and in situ T cell response. Gene expression profiling studies have clearly isolated a well-known subgroup of CRC characterized by microsatellite instability (MSI) CRC, associated with a strong immune response signature involving both Th1/cytotoxic and immune evasion pathways. Moreover, the investigators have previously shown that HLA-E/β2m is overexpressed by tumor cells in roughly 20% of CRC and is associated with a worse prognosis, most likely due to NK and T effector cell functions upon engagement with the inhibitory NK receptor CD94/NKG2A. However, our recent results on an enlarger cohort of patients suggest that if this observation holds true for MSS CRC, HLA-E over-expression is inversely associated with a good prognosis in MSI CRC. Thus, the phenotype and function of TIL, depending on the MSI/MSS status of CRC have to be precised. The investigators hypothesized that in MSI CRC, known to express a high number of MSI-H related frameshift peptides which represent a pool of tumor specific antigens, HLA-E could present peptides to TCR of non conventional CD8+ HLA-E-restricted alpha-betaT cells (also expressing CD94), then inducing a strong antitumor cytolytic activity. Therefore, the aim of this project is to determine the exact phenotype, function and specificity of the CD94+ TIL in CRC, depending on both the HLA-E and the MSI/MSS status of tumor cells. These results could impact the clinical practice as anti-NKG2A monoclonal antibodies or frameshift peptide based immunotherapy that could be promising new therapeutic options in CRC patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group "patients with colorectal cancer" | – | Other: Non interventional studyMajor patients treated surgically for colorectal cancer at Nantes University Hospital or at the Institut de Cancerologie de l'Ouest and agreeing to participate in the study |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Major patients treated surgically for colorectal cancer at the Nantes University Hospital or the West Institute of Cancerology
Key inclusion criteria (6 listed)
- Major patients treated surgically for colorectal cancer at the Nantes University Hospital or the West Institute of Cancerology
- Patients agreeing to participate in the study
- Age> 85 years
- Neoadjuvant or immunosuppressive therapy for other pathology
- Size of the tumor insufficient to carry out all the samples dedicated to the research without constraining the diagnostic step (tumoral sampling at least equal to 1 cm3)
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| Non interventional study | Other | Group "patients with colorectal cancer" |
Primary outcome
The phenotype of TIL will be precised by immunohistochemisry and flow cytometry using various combinations of monoclonal antibodies to identify different subset of TIL and their frequency, especially those expressing NKG2A or NKG2C chain.
Time frame: Until 5 years
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 18 Apr 2019.
- Individual participant dataSharing planned: No
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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.
Céline BOSSARD, Pr principal investigator
Nantes University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of ColoRectal Cancer, run by Nantes University Hospital at 1 site in France.
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 6 inclusion and 0 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 18 Apr 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 France. 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.
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?
The phenotype of TIL will be precised by immunohistochemisry and flow cytometry using various combinations of monoclonal antibodies to identify different subset of TIL and their frequency, especially those expressing NKG2A or NKG2C chain. (time frame: Until 5 years). 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 18 Apr 2019.