Clinical trial NCT06952101: A Global, Integrated, Personalized, Stage-related, Multimodal Therapeutic Approach for Rectal Adenocarcinoma Based on Organ Sparing and Mininvasivity
Official title: INTERPRETE: a Global, Integrated, Personalized, Stage-related, Multimodal Therapeutic Approach for Rectal Adenocarcinoma Based on Organ Sparing and Mininvasivity
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rectal Adenocarcinoma
Non Metastatic
Keywords: Rectal Adenocarcinoma
mininvasivity
organ sparing
surgical rectal resection
Lead sponsor: Fondazione del Piemonte per l'Oncologia
Sponsor class: OTHER
First posted: 2025-04-30
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Development and Validation of a Clinical-Radiologic-Molecular Scoring System for Predicting Pathologic Complete Response (pCR) in Rectal Cancer
timeFrame: 4 Years
Secondary outcomes:
measure: Success Rate of the Organ Sparing Approach (OSA)
timeFrame: 4 Years
measure: Long-Term Disease-Free Survival in Patients Undergoing Organ Sparing Approach (OSA) vs. Radical Surgical Resection (RSR)
timeFrame: 5 Years
measure: Short-Term General Cancer-Related Quality of Life (QoL) in OSA vs. Resection Groups
timeFrame: Baseline (before CRT), Post-CRT, Post-surgery, 6-month follow-up, 12-month follow-up
measure: Short-Term Colorectal Cancer-Specific Functioning in OSA vs. Resection Groups
timeFrame: Baseline (before CRT), Post-CRT, Post-surgery, 6-month follow-up, 12-month follow-up
measure: Bowel Dysfunction After Rectal Surgery (Low Anterior Resection Syndrome - LARS) in OSA vs. Resection Groups
timeFrame: Baseline (before CRT), Post-CRT, Post-surgery, 6-month follow-up, 12-month follow-up
Other outcomes:
Locations:
city: Candiolo
country: Italy
facility: Department of Surgical Oncology - FPO-IRCCS Institute for Cancer Research and Treatment
state: Turin
Study officials:
affiliation: Fondazione del Piemonte per l'Oncologia
name: Felice Borghi, MD
role: PRINCIPAL_INVESTIGATOR
References: