Colorectal CancerNCT04323813
"High Levels of EMT-TFs for the Diagnosis of Colorectal Cancer (CRC)"
An observational study of Colorectal Cancer, run by Istituto Clinico Humanitas at 1 site in Italy.
Trial summary
The present study is aimed at detecting and measuring mRNA levels of genes involved in epithelial to mesenchymal transition (EMT) in biological samples, i.e. in peripheral blood samples of colorectal cancer (CRC) patients and healthy controls, to determine the presence of disease, its progression and risk of… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Liquid biopsy
- Type of treatment
- Injection or infusion
- How many people
- 900 participants
- Where
- 1 siteItaly
- Study dates
- 1 Sep 2017to Sep 2022
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: This is a multicenter, prospective cohort study of molecular screening for primary colon cancer. The main objectives of the trial are: 1. To develop a specific and reproducible assay for the detection colorectal cancer based on blood RNA and to amplify cancer-specific molecular markers using RT-PCR. 2. To correlate the presence of molecular markers in the samples with the presence of colon cancer or pre-cancerous lesions. 3. To add additional biomarkers to the study panel of biomarkers.
Who may be able to join
- Males or females over 18 years of age capable of providing informed consent.
- Primary, Stage I-IV [localized, node negative or node positive] colon carcinoma confirmed by tissue biopsy or colon mass, clinically consistent with cancer and eventually confirmed by pathology.
- Patients free from other neoplastic disease and related chemo / radio / adjuvant or neo-adjuvant therapies for at least 5 years, with documented complete remission.
- Controls subjects as well as healthy clean colonoscopy subjects or with hyperplastic polyps, and healthy subjects with low grade dysplasia (LGD) and high grade dysplasia (HGD) and with inflammatory bowel disease (IBD)
Who cannot join
- Patients under the age of 18 years or over the age of 80 years.
- Patients unwilling to or unable to give informed consent.
- Patients with a new metacrone tumor (post-operative for previous CRC resection within 5 years before study enrollment).
- Patients who are undergoing to "sandwich" surgery between two chemotherapeutic treatments
- Patients diagnosed with invasive cancer of other organs within 5 years before study enrollment .
- Patients with acute inflammatory diseases or under any emergency condition.
- Pregnant women.
Trial locations and contacts
1 site in 1 country.
Luana Greco, MD contact
Italy1 site, 1 recruiting
- Recruiting
Istituto Clinico Humanitas
Rozzano, Milano, 20089
Laghi AG Luigi, MD, PhD
About this study
The present study is aimed at detecting and measuring mRNA levels of genes involved in epithelial to mesenchymal transition (EMT) in biological samples, i.e. in peripheral blood samples of colorectal cancer (CRC) patients and healthy controls, to determine the presence of disease, its progression and risk of recurrence.
Read the detailed description
The investigators first provided evidence that human colorectal cancer (CRC) cells can undergo EMT during local invasion, and that EMT transcription factors (i.e.Twist family basic helix-loop-helix transcription factor 1 (TWIST1)) are increased in the blood of CRC patients. In addressing the relevance of EMT in the metastatic process, the prognostic role of M-like cancer cells entering into the circulation remains to be determined.
Currently, the notion that cancer disseminates via the circulation led to increased attention on the identification of circulating tumor cells (CTCs) in blood samples ("liquid biopsy"; LB), so far mostly based upon epithelial (E) markers. However, an un-biased evaluation of CTCs, providing meaningful information for cancer diagnosis up to therapy, cannot exclude cells with M features. LB data show that circulating TWIST1 mRNAs are significantly and steadily increased in the blood of CRC patients. These findings indicate that EMT players in the circulation change during different phases of CRC progression.
The present study is aimed at detecting and measuring messenger ribonucleic acid (mRNA) levels of genes involved in epithelial to mesenchymal transition in biological samples, i.e. in peripheral blood samples of tumor patients, to determine the presence of disease, its progression and possibly the risk of recurrence, even in patients who will be treated with adjuvant therapy on clinical ground.
Aim of this study is to depict the molecular profile of EMT transcription factor (EMT-TFs) variations in the blood of patients with early, intermediate or advanced CRC, with respect to disease progression and delivered treatments.
Primary endpoint: To determ the stage, the remission or the progression of a colorectal cancer in a colorectal cancer affected subject not administered with an appropriate antitumor treatment (e.g., neo-adjuvant therapy) comprising the step of assaying a biological sample from said subject for the presence of a panel of mRNAs encoding for transcription factors involved in epithelial to mesenchymal transition.
Secondary endpoint: To identify biomarkers suitable for the selection of patients amenable of responsiveness to medical and surgical treatment.
- Conditions
- Colorectal Cancer
- Being tested
- Liquid biopsy
- Keywords
- Epithelial to Mesenchymal Transition, EMT, CRC, mRNA, EMT-TF, Diagnosis, Biomarkers, Liquid biopsy
- Medical subject headings
- Colorectal Neoplasms, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liquid biopsyDiagnostic test
Detection and quantification of EMT-transcription factor mRNA levels in blood
| Study group | Role | What they receive |
|---|---|---|
| Cases | CRC patients: primary, Stage I-IV (localized, node negative or node positive) colon carcinoma confirmed by tissue biopsy, and patients with advanced adenoma (including high-grade dysplasia, HGD). Receives: Diagnostic Test: Liquid biopsy | |
| Controls | Controls subjects as well as healthy clean colonoscopy subjects or with hyperplastic polyps, and healthy subjects with diminutive adenoma-low grade dysplasia (LGD) and with inflammatory bowel disease (IBD). Receives: Diagnostic Test: Liquid biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessments of diagnosis of CRC by EMT-TF mRNA levels in blood
To determine the stage, the remission or the progression of a colorectal cancer in a colorectal cancer affected subject not administered with an appropriate antitumor treatment (e.g., neo-adjuvant therapy) comprising the step of assaying a biological sample from said subject for the presence of a panel of mRNAs encoding for transcription factors involved in epithelial to mesenchymal transition.
Measured: Analysis at day 0: at diagnosis or before surgery for CRC patients; before colonoscopy in controls
Secondary outcomes (1)
Prediction of prognosis of CRC by EMT-TF mRNA levels in blood
To identify biomarkers suitable for the selection of CRC patients amenable of responsiveness to medical and surgical treatment.
Measured: Analysis at least: 7-15 days from surgery (T1), 30 days (T2) from surgery, 6 months (T3) from surgery, 1 year (T4) from surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2020
- Study start1 Sep 2017
- Primary completionSep 2021 (estimated)
- Study completionSep 2022 (estimated)
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 Istituto Clinico HumanitasThe 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 900 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituto Clinico Humanitas
- Sponsor type
- University, hospital or other
- Collaborators
- Cliniche Gavazzeni spa - Bergamo (BG), Istituto Clinico Mater Domini - Castellanza (VA), Humanitas Gradenigo - Torino
- Responsible party
- Sponsor
- Investigators
- Luigi AG Laghi, MD, PhD, Principal investigator, Humanitas Clinical Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04323813
- Sponsor's protocol ID
- EMT CRC 1.1
- Status last verified
- Mar 2020
- First submitted
- 19 Dec 2019
- Last updated
- 27 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Data patent covered. No. Patent: EP13197367.9 - December 16, 2013
Publications
Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, Doni A, Marra G, Roncalli M, Mantovani A, Malesci A, Laghi L. Presence of Twist1-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors. Gastroenterology. 2013 Sep;145(3):647-57.e15. doi: 10.1053/j.gastro.2013.05.011. Epub 2013 May 15.
PubMed 23684708
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- "High Levels of EMT-TFs for the Diagnosis of Colorectal Cancer (CRC)"
- ClinicalTrials.gov ID
- NCT04323813
- Acronym / sponsor ID
- EMT CRC 1.1
- Conditions
- Colorectal Cancer
- Keywords
- Epithelial to Mesenchymal Transition, EMT, CRC, mRNA, EMT-TF, Diagnosis, Biomarkers, Liquid biopsy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 900 participants (estimated)
- Lead sponsor
- Istituto Clinico HumanitasUniversity, hospital or other
- Collaborators
- Cliniche Gavazzeni spa - Bergamo (BG), Istituto Clinico Mater Domini - Castellanza (VA), Humanitas Gradenigo - Torino
- Study start
- 1 Sep 2017 (actual)
- Primary completion
- Sep 2021 (estimated)
- Study completion
- Sep 2022 (estimated)
- First posted
- 27 Mar 2020 (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.
The present study is aimed at detecting and measuring mRNA levels of genes involved in epithelial to mesenchymal transition (EMT) in biological samples, i.e. in peripheral blood samples of colorectal cancer (CRC) patients and healthy controls, to determine the presence of disease, its progression and risk of recurrence.
Detailed description
The investigators first provided evidence that human colorectal cancer (CRC) cells can undergo EMT during local invasion, and that EMT transcription factors (i.e.Twist family basic helix-loop-helix transcription factor 1 (TWIST1)) are increased in the blood of CRC patients. In addressing the relevance of EMT in the metastatic process, the prognostic role of M-like cancer cells entering into the circulation remains to be determined.
Currently, the notion that cancer disseminates via the circulation led to increased attention on the identification of circulating tumor cells (CTCs) in blood samples ("liquid biopsy"; LB), so far mostly based upon epithelial (E) markers. However, an un-biased evaluation of CTCs, providing meaningful information for cancer diagnosis up to therapy, cannot exclude cells with M features. LB data show that circulating TWIST1 mRNAs are significantly and steadily increased in the blood of CRC patients. These findings indicate that EMT players in the circulation change during different phases of CRC progression.
The present study is aimed at detecting and measuring messenger ribonucleic acid (mRNA) levels of genes involved in epithelial to mesenchymal transition in biological samples, i.e. in peripheral blood samples of tumor patients, to determine the presence of disease, its progression and possibly the risk of recurrence, even in patients who will be treated with adjuvant therapy on clinical ground.
Aim of this study is to depict the molecular profile of EMT transcription factor (EMT-TFs) variations in the blood of patients with early, intermediate or advanced CRC, with respect to disease progression and delivered treatments.
Primary endpoint: To determ the stage, the remission or the progression of a colorectal cancer in a colorectal cancer affected subject not administered with an appropriate antitumor treatment (e.g., neo-adjuvant therapy) comprising the step of assaying a biological sample from said subject for the presence of a panel of mRNAs encoding for transcription factors involved in epithelial to mesenchymal transition.
Secondary endpoint: To identify biomarkers suitable for the selection of patients amenable of responsiveness to medical and surgical treatment.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cases | – | Diagnostic Test: Liquid biopsyCRC patients: primary, Stage I-IV (localized, node negative or node positive) colon carcinoma confirmed by tissue biopsy, and patients with advanced adenoma (including high-grade dysplasia, HGD). |
| Controls | – | Diagnostic Test: Liquid biopsyControls subjects as well as healthy clean colonoscopy subjects or with hyperplastic polyps, and healthy subjects with diminutive adenoma-low grade dysplasia (LGD) and with inflammatory bowel disease (IBD). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- This is a multicenter, prospective cohort study of molecular screening for primary colon cancer. The main objectives of the trial are: 1. To develop a specific and reproducible assay for the detection colorectal cancer based on blood RNA and to amplify cancer-specific molecular markers using RT-PCR. 2. To correlate the presence of molecular markers in the samples with the presence of colon cancer or pre-cancerous lesions. 3. To add additional biomarkers to the study panel of biomarkers.
Key inclusion criteria (4 listed)
- Males or females over 18 years of age capable of providing informed consent.
- Primary, Stage I-IV [localized, node negative or node positive] colon carcinoma confirmed by tissue biopsy or colon mass, clinically consistent with cancer and eventually confirmed by pathology.
- Patients free from other neoplastic disease and related chemo / radio / adjuvant or neo-adjuvant therapies for at least 5 years, with documented complete remission.
- Controls subjects as well as healthy clean colonoscopy subjects or with hyperplastic polyps, and healthy subjects with low grade dysplasia (LGD) and high grade dysplasia (HGD) and with inflammatory bowel disease (IBD)
Key exclusion criteria (7 listed)
- Patients under the age of 18 years or over the age of 80 years.
- Patients unwilling to or unable to give informed consent.
- Patients with a new metacrone tumor (post-operative for previous CRC resection within 5 years before study enrollment).
- Patients who are undergoing to "sandwich" surgery between two chemotherapeutic treatments
- Patients diagnosed with invasive cancer of other organs within 5 years before study enrollment .
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 |
|---|---|---|
| Liquid biopsyDetection and quantification of EMT-transcription factor mRNA levels in blood | Diagnostic test | Cases, Controls |
Primary outcome
Assessments of diagnosis of CRC by EMT-TF mRNA levels in blood
Time frame: Analysis at day 0: at diagnosis or before surgery for CRC patients; before colonoscopy in controls
To determine the stage, the remission or the progression of a colorectal cancer in a colorectal cancer affected subject not administered with an appropriate antitumor treatment (e.g., neo-adjuvant therapy) comprising the step of assaying a biological sample from said subject for the presence of a panel of mRNAs encoding for transcription factors involved in epithelial to mesenchymal transition.
1 secondary outcome
Prediction of prognosis of CRC by EMT-TF mRNA levels in blood
Time frame: Analysis at least: 7-15 days from surgery (T1), 30 days (T2) from surgery, 6 months (T3) from surgery, 1 year (T4) from surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2020.
- Results publication: PubMed 23684708Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, Doni A, Marra G, Roncalli M, Mantovani A, Malesci A, Laghi L. Presence of Twist1-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors. Gastroenterology. 2013 Sep;145(3):647-57.e15. doi: 10.1053/j.gastro.2013.05.011. Epub 2013 May 15.
- Individual participant dataSharing planned: No. Data patent covered. No. Patent: EP13197367.9 - December 16, 2013
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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.
Luana Greco, MD contact
Luigi AG Laghi, MD, PhD principal investigator
Humanitas Clinical Institute
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 Istituto Clinico Humanitas at 1 site in Italy.
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 4 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: status not confirmed, as of the sponsor's last update on 27 Mar 2020. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Luigi AG Laghi, MD, PhD (02 8224 ext. 4572, luigi.laghi@humanitas.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessments of diagnosis of CRC by EMT-TF mRNA levels in blood (time frame: Analysis at day 0: at diagnosis or before surgery for CRC patients; before colonoscopy in controls). 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 NCT04323813, 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 27 Mar 2020.