A Global, Integrated, Personalized, Stage-related, Multimodal Therapeutic Approach for Rectal Adenocarcinoma Based on Organ Sparing and Mininvasivity

NCT06952101 | Recruiting DMC

• 1 other identifier: 001-FPO24
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

A phase II, single-center, non-profit, interventional study on patients affected by rectal adenocarcinoma. Patients will be stratified into three groups based on pre-treatment clinical stage. The study investigates and may propose a comprehensive, stage-specific, multimodal approach to rectal adenocarcinoma, with a focus on organ preservation even in early stages (cT1-2N0). When organ-sparing strategies are not feasible, the approach prioritizes minimally invasive techniques (laparoscopic and robotic) to reduce the physical, psychological, and quality-of-life impact on patients.

Conditions

Rectal Adenocarcinoma; Non Metastatic

Keywords

Rectal Adenocarcinoma; mininvasivity; organ sparing; surgical rectal resection

Outcome Measures

Primary Outcomes (1)

• Development and Validation of a Clinical-Radiologic-Molecular Scoring System for Predicting Pathologic Complete Response (pCR) in Rectal Cancer

  Quantification of the probability of achieving pathologic complete response (pCR) following chemoradiotherapy (CRT) through a composite scoring system integrating: Radiomic data from Pelvic MRI and PET Endoscopic findings (e.g., mucosal healing, residual lesion) Molecular markers (e.g., Microsatellite Instability \[MSI\], mutations in BER, SSB, and NER DNA repair pathways). Scoring Output: Probability value (0-1) or risk class (low, intermediate, high) for likelihood of pCR. Purpose: Stratify patients into low- or high-probability groups to support treatment decision-making (e.g., immediate surgery vs. organ-sparing strategies).

  4 Years

Secondary Outcomes (5)

• Success Rate of the Organ Sparing Approach (OSA)

  4 Years

• Long-Term Disease-Free Survival in Patients Undergoing Organ Sparing Approach (OSA) vs. Radical Surgical Resection (RSR)

  5 Years

• Short-Term General Cancer-Related Quality of Life (QoL) in OSA vs. Resection Groups

  Baseline (before CRT), Post-CRT, Post-surgery, 6-month follow-up, 12-month follow-up

• Short-Term Colorectal Cancer-Specific Functioning in OSA vs. Resection Groups

  Baseline (before CRT), Post-CRT, Post-surgery, 6-month follow-up, 12-month follow-up

• Bowel Dysfunction After Rectal Surgery (Low Anterior Resection Syndrome - LARS) in OSA vs. Resection Groups

  Baseline (before CRT), Post-CRT, Post-surgery, 6-month follow-up, 12-month follow-up

Study Arms (3)

Sparing Approach

EXPERIMENTAL

Group 1 - Patients with high-risk pT1cN0M0 cancerized adenoma, diagnosed through histological analysis following Endoscopic Resection (ER) or Local Excision (LE). For patients classified as "high-risk" pT1 at final pathology, an experimental sparing strategy is proposed, consisting of experimental chemoradiotherapy (spCRT) followed by a Watch and Wait (W\&W) approach (also referred to as Organ-Sparing Approach, OSA), in selected cases.

Procedure: Sparing Approach

Experimental Chemoradiotherapy: A Path to Conservative Treatment

EXPERIMENTAL

Group 2 - Patients with cT2N0 tumors, typically candidates for upfront radical rectal resection. An alternative, non-operative approach is proposed based on experimental chemoradiotherapy (spCRT). According to current literature, the pathologic Complete Response (pCR) rate following CRT significantly exceeds the 25% commonly reported for intermediate to advanced rectal tumors. Clinical Complete Response (cCR) or clinical Minimal Residual disease (cMR) will be assessed through multidisciplinary, high-resolution restaging, including: Pelvic Magnetic Resonance Imaging (MRI) Positron Emission Tomography (PET) Thoraco-abdominal Computed Tomography (CT) Endorectal Ultrasound (ERUS) Rectoscopy In patients achieving cCR or cMR, a Watch \& Wait (W\&W) strategy or Local Excision/Transanal Minimally Invasive Surgery (LE/TAMIS) may be proposed to avoid the physical and psychological burden of major surgery. An intensive follow-up protocol will be implemented.

Procedure: experimental chemoradiotherapy

tandard Chemotherapy Approach: Restaging for Conservative Surgery

ACTIVE COMPARATOR

Group 3 - Patients with cT3-4, N+, CRM-positive, or EMVI-positive tumors will receive standard chemoradiotherapy (stCRT) as the initial treatment. Patients achieving cCR or cMR at restaging will be evaluated for organ-sparing strategies, including Watch \& Wait (W\&W) or LE/TAMIS, in accordance with existing multicenter clinical research protocols. In cases where a conservative approach is not feasible, standard surgical treatment will follow.

Procedure: Standard Chemotherapy

Interventions

Sparing Approach PROCEDURE

Accurate staging with Pelvic MRI, CT scan, PET total body have to be performed before local excision in order to exclude false positive mesorectal lymph nodes. Subsequent Wait and See (W\&S) approach could be proposed.

Sparing Approach

experimental chemoradiotherapy PROCEDURE

Participants with cT2N0 rectal tumors are typically candidates for upfront surgical resection. The investigators propose an alternative approach based on experimental chemoradiotherapy (spCRT). Literature suggests that pathologic complete response (pCR) rates after CRT are significantly higher than the 25% described for intermediate-advanced tumors. The investigators will assess clinical complete response (cCR) or complete metabolic response (cMR) through a multidisciplinary restaging process, including MRI, PET, thorax-abdomen CT scan, ERUS, and rectoscopy. In participants achieving cCR or cMR, a Watch and Wait (W\&S) strategy or Local Excision/Transanal Minimally Invasive Surgery (LE/TAMIS) may be proposed to avoid the physical and psychological consequences of major surgery, followed by a rigorous surveillance program.

Experimental Chemoradiotherapy: A Path to Conservative Treatment

Standard Chemotherapy PROCEDURE

Tumors will be initially treated with standard CRT (stCRT). Patients who reach cCR-cMR at restaging they are already candidates to sparing approaches with W\&S/LE/TAMIS according to Multicentric Resarch Study Protocol

tandard Chemotherapy Approach: Restaging for Conservative Surgery

Eligibility Criteria

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

You may qualify if:

• Patients aged ≥18 yrs old
• Patients able to sign the informed consent
• Patients with High Risk pT1 rectal adenocarcinoma endoscopically excised
• Patients with cT2-3aN0 rectal adenocarcinoma who has complete/major response to EXPERIMENTAL CRT
• Patients with cT3b4N0-1 rectal adenocarcinoma who has complete/major response to STANDARD CRT

You may not qualify if:

• cT2-4 any NM0 who don't reach cCR or cMR after experimental/standard CRT
• Pregnancy

Sponsors & Collaborators

• Fondazione del Piemonte per l'Oncologia: lead

Study Sites (1)

Department of Surgical Oncology - FPO-IRCCS Institute for Cancer Research and Treatment

Candiolo, Turin, 10060, Italy

RECRUITING

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

Study Officials

• Felice Borghi, MD

  Fondazione del Piemonte per l'Oncologia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alfredo Mellano, MD

CONTACT

+390119933445; alfredo.mellano@ircc.it

Annamaria Nuzzo, PHD

CONTACT

annamaria.nuzzo@ircc.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2025
• First Posted: April 30, 2025
• Study Start: April 30, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)