Rectal CancerNCT05457075
Immune Checkpoints in Predicting Response to Neoadjuvant Therapy in Rectal Cancer
An observational study of Rectal Cancer, run by Istanbul Training and Research Hospital at 1 site in Turkey (Türkiye).
Trial summary
Colorectal cancer is the third most frequently diagnosed type of cancer in the world. Recent developments in the treatment of cancers suggest that immune checkpoint inhibitors will play an important role. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Immune checkpoint measure
- How many people
- 38 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 1 May 2022to 15 Feb 2023
- 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 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients who were diagnosed with stage II-III rectal cancer in the General Surgery outpatient clinic of Istanbul Training and Research Hospital between May 2022 and October 2022 and required neoadjuvant treatment
Who may be able to join
- Over 18 years old,
- Patients who will receive neoadjuvant therapy with clinically and histopathologically proven stage II-III rectal cancer
Who cannot join
- Known immunodeficiency
- Having a primary malignancy other than rectal cancer,
- Pregnants,
- Patients younger than 18 years and older than 90 years,
- Patients who refused to participate in the study
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Istanbul Training and Research Hospital
Istanbul, 34098
About this study
Official title: Role of Immune Checkpoints in Predicting Response to Neoadjuvant Therapy in Rectal Cancer Patients
Colorectal cancer is the third most frequently diagnosed type of cancer in the world. Recent developments in the treatment of cancers suggest that immune checkpoint inhibitors will play an important role. Many studies have documented many types of soluble receptors and ligands that can be detected in plasma in cancer, and plasma levels of these molecules correlate with cancer severity. There is only one study in the literature evaluating the status of soluble immune control points in patients with rectal cancer. The aim of this study is to investigate the role of serum immune checkpoints before neoadjuvant therapy in predicting clinical response in patients with rectal cancer. In this way, it is aimed to show whether immune checkpoints are predictive markers that can predict response to neoadjuvant therapy in patients with stage II-III rectal cancer.
Read the detailed description
Colorectal cancers are the third most frequently diagnosed cancer type in the world. Recent developments in the treatment of cancers suggest that immune checkpoint inhibitors will play an important role. Among the different immune checkpoint treatments, those containing PD-1 and CTLA-4 stand out as the most effective ones. In clinical trials, anti-CTLA-4 antibody and anti-PD-1 antibody showed great promise by significantly improving overall survival in newly diagnosed and patients who had neoadjuvant treatment against a wide range of solid and hematological malignancies. However, the effects of soluble receptors and ligands on immune system regulation and cancer therapy have been less studied. Soluble receptors and ligands, which are part of a family that includes full-length receptors and ligands, are produced by mRNA expression or cleavage of membrane-bound proteins and are found free in plasma. These structures may play important roles in immune system regulation through interactions between soluble receptors and full-length ligands or between soluble ligands and full-length receptors. Many studies have documented many types of soluble receptors and ligands that can be detected in plasma in cancer patients, and plasma levels of these molecules correlate with cancer severity. As soluble molecules, serum and tissue levels can be easily detected. These molecules are also critical factors for assessing the severity and prognosis of cancer and many other diseases.
In a study, the amounts of PD-L1 and CTLA-4 both on the tumor and soluble in the blood were evaluated, and the high levels of PD-L1 and CTLA-4 were associated with a poor prognosis.
There is only one study in the literature evaluating the status of soluble immune control points in patients with rectal cancer. Of many immune control points, only PD-1 and PD-L1 were evaluated in this study.
In this study, it is planned to include patients who were diagnosed with stage II-III rectal cancer in the General Surgery outpatient clinic of Istanbul Training and Research Hospital between May 2022 and October 2022 and required neoadjuvant treatment in their examinations. Routine rectal cancer surgery will be performed after neoadjuvant treatment of the patients included in the study, and their pathology reports will be examined, and tumor regression scores will be evaluated. Before neoadjuvant treatment, 10 cc of blood will be collected from the patients in a biochemistry tube, their serum will be separated by centrifugation and stored in a -80oC refrigerator. After the collection of all samples, serum immune control points will be evaluated by flow cytometry from the samples.
Thus, it will be determined whether there is any relationship between serum immune checkpoint levels and tumor regression score.
- Conditions
- Rectal Cancer
- Being tested
- Immune checkpoint measure
- Keywords
- Neoadjuvant Therapy, Rectal Cancer, Immune Checkpoints
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immune checkpoint measureDiagnostic test
The measurement of soluble immune checkpoints of stage II-III rectal cancer before neoadjuvant treatment
| Study group | Role | What they receive |
|---|---|---|
| Case | Stage II-III rectal cancer patients who have neoadjuvant therapy Receives: Diagnostic Test: Immune checkpoint measure |
What is being measured
The primary outcome is the main question the study is designed to answer.
Soluble immune checkpoints
sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9
Measured: Before neoadjuvant treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2022
- Study start1 May 2022
- Primary completion1 Dec 2022
- Study completion15 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Rectal 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
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istanbul Training and Research Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Ufuk Oguz Idiz, Istanbul Training and Research Hospital
- Investigators
- Ufuk Oguz Idiz, Assoc.Prof., Principal investigator, Istanbul Training and Reseach Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05457075
- Sponsor's protocol ID
- Neoadjuvant rectum
- Status last verified
- May 2023
- First submitted
- 9 Jul 2022
- Last updated
- 9 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Tominaga T, Akiyoshi T, Yamamoto N, Taguchi S, Mori S, Nagasaki T, Fukunaga Y, Ueno M. Clinical significance of soluble programmed cell death-1 and soluble programmed cell death-ligand 1 in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. PLoS One. 2019 Feb 26;14(2):e0212978. doi: 10.1371/journal.pone.0212978. eCollection 2019.
PubMed 30807610Sasidharan Nair V, Toor SM, Taha RZ, Shaath H, Elkord E. DNA methylation and repressive histones in the promoters of PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, PD-L1, and galectin-9 genes in human colorectal cancer. Clin Epigenetics. 2018 Aug 6;10(1):104. doi: 10.1186/s13148-018-0539-3.
PubMed 30081950Omura Y, Toiyama Y, Okugawa Y, Yin C, Shigemori T, Kusunoki K, Kusunoki Y, Ide S, Shimura T, Fujikawa H, Yasuda H, Hiro J, Ohi M, Kusunoki M. Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients. Cancer Immunol Immunother. 2020 Dec;69(12):2533-2546. doi: 10.1007/s00262-020-02645-1. Epub 2020 Jun 23.
PubMed 32577816
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Immune Checkpoints in Predicting Response to Neoadjuvant Therapy in Rectal Cancer Patients
- ClinicalTrials.gov ID
- NCT05457075
- Acronym / sponsor ID
- Neoadjuvant rectum
- Conditions
- Rectal Cancer
- Keywords
- Neoadjuvant Therapy, Rectal Cancer, Immune Checkpoints
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Istanbul Training and Research HospitalOther government
- Study start
- 1 May 2022 (actual)
- Primary completion
- 1 Dec 2022 (actual)
- Study completion
- 15 Feb 2023 (actual)
- First posted
- 13 Jul 2022 (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.
Colorectal cancer is the third most frequently diagnosed type of cancer in the world. Recent developments in the treatment of cancers suggest that immune checkpoint inhibitors will play an important role. Many studies have documented many types of soluble receptors and ligands that can be detected in plasma in cancer, and plasma levels of these molecules correlate with cancer severity. There is only one study in the literature evaluating the status of soluble immune control points in patients with rectal cancer. The aim of this study is to investigate the role of serum immune checkpoints before neoadjuvant therapy in predicting clinical response in patients with rectal cancer. In this way, it is aimed to show whether immune checkpoints are predictive markers that can predict response to neoadjuvant therapy in patients with stage II-III rectal cancer.
Detailed description
Colorectal cancers are the third most frequently diagnosed cancer type in the world. Recent developments in the treatment of cancers suggest that immune checkpoint inhibitors will play an important role. Among the different immune checkpoint treatments, those containing PD-1 and CTLA-4 stand out as the most effective ones. In clinical trials, anti-CTLA-4 antibody and anti-PD-1 antibody showed great promise by significantly improving overall survival in newly diagnosed and patients who had neoadjuvant treatment against a wide range of solid and hematological malignancies. However, the effects of soluble receptors and ligands on immune system regulation and cancer therapy have been less studied. Soluble receptors and ligands, which are part of a family that includes full-length receptors and ligands, are produced by mRNA expression or cleavage of membrane-bound proteins and are found free in plasma. These structures may play important roles in immune system regulation through interactions between soluble receptors and full-length ligands or between soluble ligands and full-length receptors. Many studies have documented many types of soluble receptors and ligands that can be detected in plasma in cancer patients, and plasma levels of these molecules correlate with cancer severity. As soluble molecules, serum and tissue levels can be easily detected. These molecules are also critical factors for assessing the severity and prognosis of cancer and many other diseases.
In a study, the amounts of PD-L1 and CTLA-4 both on the tumor and soluble in the blood were evaluated, and the high levels of PD-L1 and CTLA-4 were associated with a poor prognosis.
There is only one study in the literature evaluating the status of soluble immune control points in patients with rectal cancer. Of many immune control points, only PD-1 and PD-L1 were evaluated in this study.
In this study, it is planned to include patients who were diagnosed with stage II-III rectal cancer in the General Surgery outpatient clinic of Istanbul Training and Research Hospital between May 2022 and October 2022 and required neoadjuvant treatment in their examinations. Routine rectal cancer surgery will be performed after neoadjuvant treatment of the patients included in the study, and their pathology reports will be examined, and tumor regression scores will be evaluated. Before neoadjuvant treatment, 10 cc of blood will be collected from the patients in a biochemistry tube, their serum will be separated by centrifugation and stored in a -80oC refrigerator. After the collection of all samples, serum immune control points will be evaluated by flow cytometry from the samples.
Thus, it will be determined whether there is any relationship between serum immune checkpoint levels and tumor regression score.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Case | – | Diagnostic Test: Immune checkpoint measureStage II-III rectal cancer patients who have neoadjuvant therapy |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who were diagnosed with stage II-III rectal cancer in the General Surgery outpatient clinic of Istanbul Training and Research Hospital between May 2022 and October 2022 and required neoadjuvant treatment
Key inclusion criteria (2 listed)
- Over 18 years old,
- Patients who will receive neoadjuvant therapy with clinically and histopathologically proven stage II-III rectal cancer
Key exclusion criteria (5 listed)
- Known immunodeficiency
- Having a primary malignancy other than rectal cancer,
- Pregnants,
- Patients younger than 18 years and older than 90 years,
- Patients who refused to participate in the study
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 |
|---|---|---|
| Immune checkpoint measureThe measurement of soluble immune checkpoints of stage II-III rectal cancer before neoadjuvant treatment | Diagnostic test | Case |
Primary outcome
Soluble immune checkpoints
Time frame: Before neoadjuvant treatment
sCD25 (IL-2Ra), 4-1BB, B7.2 (CD86), Free Active TGF-β1, CTLA-4, PD-L1, PD-1, Tim-3, LAG-3, Galectin-9
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 9 May 2023.
- Background: PubMed 30807610Tominaga T, Akiyoshi T, Yamamoto N, Taguchi S, Mori S, Nagasaki T, Fukunaga Y, Ueno M. Clinical significance of soluble programmed cell death-1 and soluble programmed cell death-ligand 1 in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. PLoS One. 2019 Feb 26;14(2):e0212978. doi: 10.1371/journal.pone.0212978. eCollection 2019.
- Results publication: PubMed 30081950Sasidharan Nair V, Toor SM, Taha RZ, Shaath H, Elkord E. DNA methylation and repressive histones in the promoters of PD-1, CTLA-4, TIM-3, LAG-3, TIGIT, PD-L1, and galectin-9 genes in human colorectal cancer. Clin Epigenetics. 2018 Aug 6;10(1):104. doi: 10.1186/s13148-018-0539-3.
- Results publication: PubMed 32577816Omura Y, Toiyama Y, Okugawa Y, Yin C, Shigemori T, Kusunoki K, Kusunoki Y, Ide S, Shimura T, Fujikawa H, Yasuda H, Hiro J, Ohi M, Kusunoki M. Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients. Cancer Immunol Immunother. 2020 Dec;69(12):2533-2546. doi: 10.1007/s00262-020-02645-1. Epub 2020 Jun 23.
- Individual participant dataSharing planned: Undecided
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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.
Ufuk Oguz Idiz, Assoc.Prof. principal investigator
Istanbul Training and Reseach 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 Rectal Cancer, run by Istanbul Training and Research Hospital at 1 site in Turkey (Türkiye).
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 2 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 9 May 2023. 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 Turkey (Türkiye). 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?
Soluble immune checkpoints (time frame: Before neoadjuvant treatment). 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 NCT05457075, which also lists 3 linked publications.
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 9 May 2023.