Timisnar - Biomarkers Substudy (Timisnar-mirna)

NCT03962088 | Recruiting DMC

• 1 other identifier: A19
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant chemoradiotherapy (nCHT) followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage in the primary tumor and lymph nodes (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading (TRG) and lymph node status (ypN) helped to visualize individual tumor sensitivity to CRT retrospectively. Since the response to nCHT is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed. As a potential alternative to CEA and ctDNA, microRNAs (miRNAs) are currently under investigation to serve as blood-based biomarkers. miRNAs are small, noncoding RNAs that regulate gene expression by post-transcriptional mRNA binding, which promotes the destabilization of target miRNAs. The target specificity of miRNAs is largely predetermined by their so-called "seed-sequence" (containing nucleotides at position 2-7 of the miRNA). They are highly conserved between species, stable and easy detectable even in small concentrations. They have been widely analyzed in physiological and pathological processes, and their expression is tissue specific.

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (1)

• Change in expression levels of plasma miRNA

  the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pCR

  5 years

Secondary Outcomes (2)

• miRNA expression and surgery

  5 years

• miRNA expression and surveillance

  5 years

Interventions

miRNA DIAGNOSTIC_TEST

15 ml of whole blood samples are collected in Vacutainer tubes with spray-coated K2EDTA and stored at room temperature. To minimize the hemolysis and nucleic acids degradation, plasma separation undergoes within 2 h. Within 1 h, tubes are subjected to a first centrifugation step at 2200 x g and room temperature for 15 min. Plasma supernatants are transferred to 15 mL tubes, carefully avoiding contact with the lymphocytic ring, and tubes are centrifuged a second time at 3000 x g and RT for 10 min to remove cellular debris. Plasma samples are then collected into 1.5 mL cryovials and all the aliquots are stored at -80 °C.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All included patients in the TiMiSNAR Trial (already approved by local Ethical Committees on 8/5/2018 - NCT3465982) are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery and after adjuvant chemotherapy whenever indicated.

You may qualify if:

• Age \>18 years
• cT3/4N0/+M0 confirmed on CT-scan, MRI (stratification for T3a-b-c-d)
• Histologically-proven adenocarcinoma of the rectum
• Eligible for a resective surgery with TME
• Eligible for chemoradiation treatment

You may not qualify if:

• Metastatic disease
• Squamous carcinoma of the anal canal
• Unable to complete neoadjuvant treatment

Sponsors & Collaborators

• Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria: lead

Study Sites (1)

SS. Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

RECRUITING

Related Publications (7)

• Yu J, Li N, Wang X, Ren H, Wang W, Wang S, Song Y, Liu Y, Li Y, Zhou X, Luo A, Liu Z, Jin J. Circulating serum microRNA-345 correlates with unfavorable pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer. Oncotarget. 2016 Sep 27;7(39):64233-64243. doi: 10.18632/oncotarget.11649.

  PMID: 27572313 RESULT

• Dayde D, Tanaka I, Jain R, Tai MC, Taguchi A. Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer. Int J Mol Sci. 2017 Mar 7;18(3):573. doi: 10.3390/ijms18030573.

  PMID: 28272347 RESULT

• Rampazzo E, Del Bianco P, Bertorelle R, Boso C, Perin A, Spiro G, Bergamo F, Belluco C, Buonadonna A, Palazzari E, Lonardi S, De Paoli A, Pucciarelli S, De Rossi A. The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients. Br J Cancer. 2018 Mar 20;118(6):878-886. doi: 10.1038/bjc.2017.492. Epub 2018 Feb 15.

  PMID: 29449673 RESULT

• Augestad KM, Merok MA, Ignatovic D. Tailored Treatment of Colorectal Cancer: Surgical, Molecular, and Genetic Considerations. Clin Med Insights Oncol. 2017 Feb 16;11:1179554917690766. doi: 10.1177/1179554917690766. eCollection 2017.

  PMID: 28469509 RESULT

• Drebber U, Lay M, Wedemeyer I, Vallbohmer D, Bollschweiler E, Brabender J, Monig SP, Holscher AH, Dienes HP, Odenthal M. Altered levels of the onco-microRNA 21 and the tumor-supressor microRNAs 143 and 145 in advanced rectal cancer indicate successful neoadjuvant chemoradiotherapy. Int J Oncol. 2011 Aug;39(2):409-15. doi: 10.3892/ijo.2011.1036. Epub 2011 May 10.

  PMID: 21567082 RESULT

• Della Vittoria Scarpati G, Falcetta F, Carlomagno C, Ubezio P, Marchini S, De Stefano A, Singh VK, D'Incalci M, De Placido S, Pepe S. A specific miRNA signature correlates with complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1113-9. doi: 10.1016/j.ijrobp.2011.09.030. Epub 2011 Dec 13.

  PMID: 22172905 RESULT

• Monsellato I, Garibaldi E, Cassinotti E, Baldari L, Boni L, Elmore U, Delpini R, Rosati R, Perinotti R, Alongi F, Bertocchi E, Gori S, Ruffo G, Pernazza G, Pulighe F, De Nisco C, Morpurgo E, Contardo T, Mammano E, Perna F, Menegatti B, Coratti A, Buccianti P, Balestri R, Ceccarelli C, Cavaliere D, Solaini L, Ercolani G, Traverso E, Fusco V, Torri V, Orecchia S. Expression levels of circulating miRNAs as biomarkers during multimodal treatment of rectal cancer - TiMiSNAR-mirna: a substudy of the TiMiSNAR Trial (NCT03962088). Trials. 2020 Jul 25;21(1):678. doi: 10.1186/s13063-020-04568-9.

  PMID: 32711544 DERIVED

Related Links

• Official site of the study

Biospecimen

Retention: SAMPLES WITHOUT DNA

Total RNA, including miRNAs, are isolated using a commercial kit (miRNeasy Mini Kit, Qiagen, Hilden, Germany) according to the manufacturer's instructions. The RNA concentration is assessed using a spectrophotometer. The RNA results adequate for mRNA expression whenever its concentration is ≥30 ng/μL and its quality is acceptable if the ratio between the value of the absorbance (A) at 260 nm and the absorbance at 280 nm is ≥1.8, and the ratio between the value of absorbance (A) at 260 nm and the one at 230 nm is ≥2.

MeSH Terms

Conditions

Rectal Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Igor Monsellato, PhD

CONTACT

+390131206078; igor.monsellato@ospedale.al.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 23, 2019
• Study Start: April 1, 2019
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: April 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)