IMMUNOlogical Microenvironment in REctal Adenocarcinoma Treatment.

NCT04917263 | Unknown

• 1 other identifier: AIRC IG2019 23381 IMMUNOREACT2
• Study Type: observational
• Target: 544
• Locations: 1 country
• Sites: 1

Brief Summary

Background The current management on rectal cancer based on TNM staging has some limitations. In locally advanced rectal cancer after neoadjuvant therapy the persistence of a complete response to therapy cannot be accurately predicted by the simple tumor regression grade. The current guidelines recommend the complete rectal resection with a total mesorectal excision. The implications for patients' quality of life are evident even in case of sphincter sparing surgery. Moreover, in both cases the cancer sample available for the analysis can be small or inexistent. Hypothesis The main hypothesis underlying our research is that the aggressiveness of rectal cancer is determined by the complex interactions between the malignant cells and their immune microenvironment. The second hypothesis is that relevant trace of this cross talk between tumor cells and immune microenvironment can be detected in the normal mucosa surrounding the cancer according to the concept of field cancerization. Aims The aim of this project is to analyze the healthy rectal mucosa surrounding the cancer to identify traces of immunosurveillance mechanisms and of field cancerization and to use them to obtain a composite prognostic test to predict recurrence after complete response at neoadjuvant therapy in case of locally advanced rectal cancer. Experimental Design This prognostic test will be constructed on the combinatory analysis of the transcriptome, immune and epithelial cells cross-talk, immune checkpoints and miRNA expression in normal rectal mucosa surrounding cancer. The project aim is to identify, among locally advanced rectal cancer, those with sustained complete response to neoadjuvant chemo/radiotherapy. The study is articulated in two steps. In step A, we will retrospectively analyze archival tissue samples in order to identify the most performing biomarkers; in step B, we will validate the prognostic performance of the markers identified in phase I through a prospective analysis of rectal mucosa specimen.

Conditions

Rectal Cancer

Keywords

rectal cancer; complete response; neoadjuvant therapy; immune surveillance

Outcome Measures

Primary Outcomes (1)

• pathological complete response on the operative specimen

  pathological complete response to neoadjuvant chemo/radiotherapy in locally advanced rectal cancer

  first post operative month

Study Arms (2)

Retrospective

Diagnostic Test: Immunohistochemistry, Flow citometry, Trascriptome analysis

Prospective

Diagnostic Test: Immunohistochemistry, Flow citometry, Trascriptome analysis

Interventions

Immunohistochemistry, Flow citometry, Trascriptome analysis DIAGNOSTIC_TEST

we will perform immunohistochemistry, flow cytometry, transcriptomic analysis, mRNA microarray and mutational profiling

Prospective; Retrospective

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

We aim to analyze 66 patients with pathological complete response and 66 patients without complete response after neoadjuvant therapy for locally advanced rectal cancer. Given an expected proportion of 20% of patients with complete response, we estimate to enroll a total number of 66/0.20=330 patients with early rectal cancer. However, we will performed flow cytometry, transcriptomic analysis, mRNA microarray and mutational profiling only in 132 patients (66 patients with complete response and 66 patients without complete response) in order to test the non-inferiority of AUC. Taking into account a 15-20% of locally advanced rectal cancer patients with pathological complete response to neoadjuvant therapy and a maximum of 7 prognostic factors (including markers and clinical factors) in the model, we aim to enroll 412 patients in this part of the study.

You may qualify if:

• locally advanced (cT3-4 and/or N+, TNM stage II-III) low and medium rectal cancer (\<11 cm) or low rectum adenocarcinoma cT≤2, at risk for abdominoperineal amputation, undergoing neoadjuvant therapy will be included in the study group.
• Only neoadjuvant therapy protocols including long course radiotherapy (45 Gy) and fluoropyrimidine-based regimens will be included while short radiation therapy of radiation therapy or chemotherapy alone will be excluded
• at least 6 weeks after the end of the neoadjuvant therapy will be included
• Full availability of clinical records at least 1 year of follow up

Sponsors & Collaborators

• University of Padova: lead
• Associazione Italiana per la Ricerca sul Cancro: collaborator
• Azienda Ospedaliera di Padova: collaborator
• Istituto Oncologico Veneto IRCCS: collaborator
• Azienda ULSS 3 Serenissima: collaborator
• Azienda Ulss 2 Marca Trevigiana: collaborator

Study Sites (1)

Azienda Ospedale Università di Padova

Padua, 35128, Italy

RECRUITING

Related Publications (1)

• Becherucci G, Ruffolo C, Scarpa M, Scognamiglio F, Stepanyan A, Maretto I, Kotsafti A, De Simoni O, Pilati P, Franzato B, Scapinello A, Bergamo F, Massani M, Stecca T, Pozza A, Cataldo I, Brignola S, Pellegrini V, Fassan M, Guzzardo V, Dal Santo L, Salmaso R, Carlotta C, Dei Tos AP, Angriman I, Spolverato G, Chiminazzo V, Negro S, Vignotto C, Marchegiani F, Facci L, Rivella G, Bao QR, Baldo A, Pucciarelli S, Zizzo M, Businello G, Salmaso B, Parini D, Pirozzolo G, Recordare A, Tagliente G, Bordignon G, Merenda R, Licia L, Pozza G, Godina M, Mondi I, Verdi D, Da Lio C, Guerriero S, Piccioli A, Portale G, Zuin M, Cipollari C, Noaro G, Cola R, Candioli S, Gavagna L, Ricagna F, Ortenzi M, Guerrieri M, Tomassi M, Tedeschi U, Marinelli L, Barbareschi M, Bertalot G, Brolese A, Ceccarini L, Antoniutti M, Porzionato A, Agostini M, Cavallin F, Tussardi G, Di Camillo B, Bardini R, Castagliuolo I, Scarpa M. IMMUNOREACT 8: Immune markers of local tumor spread in patients undergoing transanal excision for clinically N0 rectal cancer. Surgery. 2025 Feb;178:108902. doi: 10.1016/j.surg.2024.09.043. Epub 2024 Nov 20.

  PMID: 39572264 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Mucosal samples from healthy tissue surrounding the cancer

MeSH Terms

Conditions

Rectal Neoplasms; Pathologic Complete Response

Interventions

Immunohistochemistry

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; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques

Study Officials

• Marco Scarpa, MD, PhD

  Clinica Chirurgica I, Azienda Ospedale Università di Padova

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marco Scarpa, MD, PhD

CONTACT

#39 049 821 2672; marco.scarpa@aopd.veneto.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: June 8, 2021
• Study Start: January 1, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: June 8, 2021

Record last verified: 2021-06

Locations

IT (1)