IMMUNOlogical Microenvironment in REctal Adenocarcinoma Treatment

NCT04915326 | Unknown

• 1 other identifier: AIRC IG2019 23381
• Study Type: observational
• Target: 466
• Locations: 1 country
• Sites: 1

Brief Summary

ABSTRACT Background The current management on rectal cancer based on TNM staging has some limitations. In early rectal cancer T stage can be not sufficient to predict the nodal status and, 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. For both cases 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 nodal metastasis in early rectal cancer and 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 aim is to predict the presence of nodal metastasis in patients with early rectal cancer. 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. Expected Results The anticipated outcome of this project is to generate one or different combination of markers to optimize rectal management and to predict rectal cancer patients outcome more accurately than traditional TNM staging or tumore regression grade. We expect to obtain a prognostic test from normal tissue that accurately predicts rectal cancer behavior even in case when the tumor samples are scarce (early rectal cancer) or absent (complete response to therapy) to avoid unnecessary total rectal excision. Impact On Cancer An immunoscore specific for rectal cancer may predict tumor progression and clinical outcome more accurately and may contribute to better design a personalized therapeutic algorithm. Moreover, nowadays patients with early rectal cancer without nodal involvement and patients with potential complete response to neoadjuvant therapy still undergo total rectal excision which is a risky procedure that impairs quality of life. The use of this new prognostic test may make possible to adopt a minimally invasive approach or even simple observation if nodal involvement or residual disease are reasonably excluded.

Conditions

Rectal Cancer Stage T1-T2; Rectal Cancer Nodal Metastasis

Outcome Measures

Primary Outcomes (1)

• Nodal metastasis in early rectalò cancer

  Predictors of nodal matastasis of early rectal cancer

  The presence of nodal metastasis will be detected at histological examination of the surgical specimen or at MRI follow up in case of minimally invasive transamnal resection at 1 year from the operation

Study Arms (2)

Retrospective

T1 and T2 rectal carcinoma operated on will be included in the study group. The first step will be a retrospective and exploratory analysis of FFPE slides retrieved from the pathology archives testing a panel of molecular marker exploring the immune reaction to the cancer (i.e. antigen presenting cells and T lymphocytes activation).

Procedure: rectal resection

Prospective

T1 and T2 rectal carcinoma operated on will be included in the study group. The second step will be a prospective and validating analysis. Tissue samples will be obtained from normal rectal mucosa adjacent to the cancer at the time of the trans anal or trans abdominal resection. In patients with early rectal cancer, the combination of immunological markers on healthy rectal mucosa adjacent to the cancer obtained in the part 1a of the study will be validated to identify the patients that will have not any nodal metastasis.

Procedure: rectal resection

Interventions

rectal resection PROCEDURE

every patients will undergo to the appropriate rectal resection

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

STEP A Taking into account a 15% of early rectal cancer patients with nodal metastasis and a maximum of 5 prognostic factors (including markers and clinical factors) in the model, we aim to enroll 334 patients in this part of the study. STEP B The sample size was calculated to demonstrate a non-inferiority of AUC with respect to an area of 0.80, assuming an AUC of 0.90 and a non-inferiority margin of 0.05. With a type I error of 0.05 and a type II error of 0.20, we aim to analyze 66 patients with lymph node metastasis (N+) and 66 patients without lymph node metastasis (N0). Given an expected proportion of 15% of N+ patients among early rectal cancer, we estimate to enroll a total number of 66/0.15=440 patients with early rectal cancer. However, we will perform flow cytometry, transcriptomic analysis, mRNA microarray and mutational profiling only in 132 patients (66 N+ and 66 N0) in order to test the non-inferiority of AUC.

Sponsors & Collaborators

• University of Padova: lead
• Associazione Italiana per la Ricerca sul Cancro: 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 (3)

• 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

• Simoni O, Scarpa M, Castagliuolo I, Stepanyan A, Angriman I, Kotsafti A, Nacci C, Scognamiglio F, Negro S, D'Angelo A, Chiminazzo V, Businello G, Ruffolo C, Salmaso R, Franzato B, Gruppo M, Pilati P, Scapinello A, Pozza A, Stecca T, Massani M, Cataldo I, Brignola S, Dei Tos AP, Ceccon C, Guzzardo V, Vignotto C, Facci L, Maretto I, Agostini M, Marchegiani F, Becherucci G, Zizzo M, Bordignon G, Merenda R, Pirozzolo G, Recordare A, Pozza G, Godina M, Mondi I, Verdi D, Lio CD, Laurino L, Saadeh L, Rivella G, Guerriero S, Romiti C, Portale G, Cipollari C, Spolverato YC, Noaro G, Cola R, Candioli S, Gavagna L, Ricagna F, Ortenzi M, Guerrieri M, Tagliente G, Tomassi M, Tedeschi U, Salmaso B, Buzzi G, Parini D, Prando D, Zuin M, Bergamo F, Zagonel V, Porzionato A, Cavallin F, Camillo BD, Cristoforo LD, Bao QR, Pucciarelli S, Bardini R, Spolverato G, Fassan M, Scarpa M; IMMUNOREACT Study Group. IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer. Cancer. 2024 Jul 1;130(13):2272-2286. doi: 10.1002/cncr.35297. Epub 2024 Apr 22.

  PMID: 38644692 DERIVED

• Spolverato G, Fassan M, Capelli G, Scarpa M, Negro S, Chiminazzo V, Kotsafti A, Angriman I, Campi M, De Simoni O, Ruffolo C, Stepanyan A, Vignotto C, Scognamiglio F, Becherucci G, Rivella G, Marchegiani F, Facci L, Bergamo F, Brignola S, Businello G, Guzzardo V, Dal Santo L, Salmaso R, Massani M, Pozza A, Cataldo I, Stecca T, Dei Tos AP, Zagonel V, Pilati P, Franzato B, Scapinello A, Pirozzolo G, Recordare A, Merenda R, Bordignon G, Guerriero S, Romiti C, Portale G, Cipollari C, Zizzo M, Porzionato A, Agostini M, Cavallin F, Di Camillo B, Bardini R, Maretto I, Castagliuolo I, Pucciarelli S, Scarpa M. IMMUNOREACT 5: female patients with rectal cancer have better immune editing mechanisms than male patients - a cohort study. Int J Surg. 2023 Mar 1;109(3):323-332. doi: 10.1097/JS9.0000000000000214.

  PMID: 37093072 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Healthy rectal mucosa sourrounding the rectal cancer

MeSH Terms

Interventions

Proctectomy

Intervention Hierarchy (Ancestors)

Surgical Procedures, Colorectal; Digestive System Surgical Procedures; Surgical Procedures, Operative

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: May 31, 2021
• First Posted: June 7, 2021
• Study Start: January 1, 2020
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: June 7, 2021

Record last verified: 2021-05

Locations

IT (1)