Clinical trial NCT04323813: "High Levels of EMT-TFs for the Diagnosis of Colorectal Cancer (CRC)"
Official title: "High Levels of EMT-TFs for the Diagnosis of Colorectal Cancer (CRC)"
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Colorectal Cancer
Keywords: Epithelial to Mesenchymal Transition
EMT
CRC
mRNA
EMT-TF
Diagnosis
Biomarkers
Liquid biopsy
Lead sponsor: Istituto Clinico Humanitas
Sponsor class: OTHER
Collaborators: name: Cliniche Gavazzeni spa - Bergamo (BG)
name: Istituto Clinico Mater Domini - Castellanza (VA)
name: Humanitas Gradenigo - Torino
First posted: 2020-03-27
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

1. Males or females over 18 years of age capable of providing informed consent.
2. 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.
3. Patients free from other neoplastic disease and related chemo / radio / adjuvant or neo-adjuvant therapies for at least 5 years, with documented complete remission.
4. 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)

Exclusion Criteria:

1. Patients under the age of 18 years or over the age of 80 years.
2. Patients unwilling to or unable to give informed consent.
3. Patients with a new metacrone tumor (post-operative for previous CRC resection within 5 years before study enrollment).
4. Patients who are undergoing to "sandwich" surgery between two chemotherapeutic treatments
5. Patients diagnosed with invasive cancer of other organs within 5 years before study enrollment .
6. Patients with acute inflammatory diseases or under any emergency condition.
7. Pregnant women.

Primary outcomes:
measure: Assessments of diagnosis of CRC by EMT-TF mRNA levels in blood
timeFrame: Analysis at day 0: at diagnosis or before surgery for CRC patients; before colonoscopy in controls
Secondary outcomes:
measure: Prediction of prognosis of CRC by EMT-TF mRNA levels in blood
timeFrame: Analysis at least: 7-15 days from surgery (T1), 30 days (T2) from surgery, 6 months (T3) from surgery, 1 year (T4) from surgery
Other outcomes:
Locations:
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milano
Study officials:
affiliation: Humanitas Clinical Institute
name: Luigi AG Laghi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.