Randomized phase II trial in patients with locally advanced rectal carcinoma

Phase 1

• Conditions: OCALLY ADVANCED RECTAL CANCER PATIENTS IN STAGE II/III; MedDRA version: 20.0Level: PTClassification code 10062099Term: Rectal neoplasmSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004385-34-IT
• Lead Sponsor: ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-10-07
• Last Update Posted: 11 January 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 340

Inclusion Criteria

Pathologically proven diagnosis of adenocarcinoma of the rectum by endoscopic biopsy within 56 days prior to randomisation.
Locally advanced tumour (defined as TNM Stage II or III) based upon the following minimum diagnostic workup: MRI of the pelvis, contrast-enhanced CT of abdomen and chest.
Able to undergo induction chemotherapy, chemoradiotherapy and total mesorectal excision (TME).
Distal part of the tumour within 0–12 cm of the anal verge (Note: intraperitoneal rectal cancer are excluded)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

Prior treatment for LARC (recurrent rectal tumours are excluded) or previous pelvic radiotherapy.
Unequivocal evidence of established metastatic disease based on minimum diagnostic workup. Patients with equivocal lesions are eligible.
Patients already taking daily aspirin and/or metformin for more than 4 weeks prior to randomisation.
Hypersensitivity to salicylic acid compounds or prostaglandin synthetase inhibitors and to any of the excipients.
Hypersensitivity to metformin or to any of the excipients

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objective is to assess the effect of each of the 3 experimental interventions (aspirin, metformin or both, in combination with neoadjuvant induction chemotherapy (ICT) and preoperative chemoradiation (CRT)) compared to standard neoadjuvant ICT;Secondary Objective: The secondary objectives are to assess the effect of the experimental interventions compared to the standard neoadjuvant treatment with ICT followed by CRT;Primary end point(s): Primary endpoint is Good Pathological Response (GPR) defined as Tumour downstaging (ypT0 or ypT1) irrespective of the pathological N stage;Timepoint(s) of evaluation of this end point: Estimated duration of recruitment: 3 years

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Tumor Regression Rate <br>•Pathological complete responses (pCR)<br>•NeoAdjuvant Rectal (NAR) score<br>•MRI Tumor Downstaging (mr TGR) rate<br>•Event-Free Survival (EFS)<br>•Overall Survival (OS)<br>•Time to Distant Recurrence (TDR) <br>•Rate of local recurrence at 3 years<br>•Abdominal Perineal Resection (APR) rate<br>•Organ preservation rate at 3 years<br>•Post-operative complications<br>•Treatment-related toxicity<br>•Quality of Life (QoL)<br>•Simplified ESMO class risk shift after induction chemotherapy;Timepoint(s) of evaluation of this end point: Estimated duration of recruitment: 3 years