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

NCT ID: NCT06952101

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-30
• Study Completion Date: 2030-12-31

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.

Detailed Description

Patients affected by rectal adenocarcinoma will be stratified into three groups according to pre-treatment clinical stage:

Group 1: pT1cN0M0 tumors may be candidates for Endoscopic Resection (ER), Local Excision (LE), or TransAnal Minimally Invasive Surgery (TAMIS). If final pathology classifies these tumors as "high-risk" pT1, patients are typically candidates for radical rectal resection due to an estimated 20% risk of mesorectal lymph node metastases. However, many patients refuse surgery and opt for direct follow-up despite the increased risk of recurrence. The investigators propose an alternative treatment with experimental chemoradiotherapy (spCRT) to reduce the risk of local relapse in patients unwilling to undergo surgery, followed by an intensive surveillance protocol. Accurate staging with pelvic MRI, CT scan, and whole-body PET must be performed prior to local excision to exclude false-positive mesorectal lymph nodes. A subsequent Watch and Wait (W&S) strategy may be considered.

Group 2: cT2N0 tumors are typically managed with upfront surgical rectal resection. This study proposes an alternative approach based on spCRT. Literature indicates that the rate of pathological Complete Response (pCR) after CRT is significantly higher than the 25% typically 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 MRI, whole-body PET, thoraco-abdominal CT scan, EndoRectal Ultrasound (ERUS), and rectoscopy. In patients achieving cCR or cMR, a W&S approach or LE/TAMIS may be proposed to minimize the psychological and physical burden of surgery, with subsequent close surveillance.

Group 3: Patients with cT3-4, N+, circumferential resection margin positive (CRM+), or extramural vascular invasion (EMVI+) tumors will initially receive standard chemoradiotherapy (stCRT). Those who achieve cCR or cMR at restaging may be considered for organ-sparing approaches (W&S/LE/TAMIS) according to established multicenter research protocols.

All patients in Group 1 and Group 2 who do not achieve cCR or cMR will be managed according to the principle of minimal invasiveness. These patients will undergo laparoscopic or robotic rectal resection with preservation of pelvic autonomic nerves, aimed at reducing genitourinary dysfunction and improving short-term outcomes (e.g., reduced postoperative pain, fewer abdominal wall hernias, faster bowel function recovery, and quicker return to daily activities). Recovery will be further optimized through integration with Enhanced Recovery After Surgery (ERAS) protocols.

Conditions

Rectal Adenocarcinoma; Non Metastatic

Keywords

Rectal Adenocarcinoma; mininvasivity; organ sparing; surgical rectal resection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sparing Approach

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.

Group Type: EXPERIMENTAL

Sparing Approach

Intervention Type: 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.

Experimental Chemoradiotherapy: A Path to Conservative Treatment

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.

Group Type: EXPERIMENTAL

experimental chemoradiotherapy

Intervention Type: 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.

tandard Chemotherapy Approach: Restaging for Conservative Surgery

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.

Group Type: ACTIVE_COMPARATOR

Standard Chemotherapy

Intervention Type: 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

Interventions

Sparing Approach

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.

Intervention Type: PROCEDURE

experimental chemoradiotherapy

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.

Intervention Type: PROCEDURE

Standard Chemotherapy

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

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione del Piemonte per l'Oncologia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Felice Borghi, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione del Piemonte per l'Oncologia

Locations

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

Candiolo, Turin, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Alfredo Mellano, MD

Role: CONTACT

Phone: +390119933445

Email: alfredo.mellano@ircc.it

Annamaria Nuzzo, PHD

Role: CONTACT

Email: annamaria.nuzzo@ircc.it

Facility Contacts

Alfredo Mellano, MD

Role: primary

Other Identifiers

001-FPO24

Identifier Type: -

Identifier Source: org_study_id