Total Neoadjuvant Treatment without Surgery for Locally Advanced Rectal Cancer: Prospective Clinical Trial to Assess Tumor Complete Response, Circulating Tumor Genetic and Epigenetic Biomarkers, and Stromal Transcriptome to Interpret Clinical Outcome (No-Cut Trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ASST Grande Ospedale Metropolitano Niguarda

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-08-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515225-28-00

EudraCT number

2017-003671-60

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To assess if the risk of distant relapse in patients managed with Induction ChemoTherapy (ICT) and Chemo-RadioTherapy (CRT) followed by NOM and intensive follow-up is clinically acceptable

Secondary objectives 1

1. - To assess whether the anticipation of standard adjuvant oxaliplatin-based chemotherapy prior to CRT increases the rate of clinical complete responses; - To assess the Local Recurrence (LR) rate, organ (rectum) preservation rate, and colostomy-free survival; - To assess Overall Survival (OS); - To assess the outcome of NOM in terms of patient-reported outcome measures [PROM] Translational Objectives, To determine association of: - 6-methylated gene panel (6-MGP) in liquid biopsy with local a/o relapse free survival; - ctDNA in liquid biopsy with local a/o relapse free survival; - stromal score in baseline tumor tissue biopsy with local response

Conditions and MedDRA coding

Adenocarcinoma of the medium/lower rectum in Stage II (cT3-4 N0) or Stage III (cT1-4, N1-2)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - Histologically confirmed diagnosis of adenocarcinoma of the medium/lower rectum - Patients must have Stage II (cT3-4 N0) or Stage III (cT1-4, N1-2) tumor - Locally advanced rectal cancer amenable to Total Mesorectal Excision (TME)/Abdominal-Perineal Amputation - No evidence of distant metastases by chest, abdomen, and pelvis contrast enhanced CT scan (TC-PET WB is acceptable alternative in patient allergic to iodate contrast medium) - No prior pelvic radiation therapy - No prior oncologic medical therapy or surgery for rectal cancer - Age >18 years - No infections requiring systemic antibiotic treatment - Performance status 0-1 (ECOG Scale) - ANC > 1.5 cell/mm3, Hb>8.0 g/ dL, PLT>150,000/mm3, total bilirubin < or equal or 1.5 x upper limit of normal, AST < or equal to three times upper limit of normal, ALT< or equal to three times upper limit of normal; Serum creatinine level < or equal to 1.5 times the upper limit of normal - Patients must read, agree to, and sign a statement of Informed Consent prior to participation - Women with childbearing potential who are negative for pregnancy test (urine or blood) and who agree to use effective contraceptive methods - Male subjects must also agree to use effective contraception

Exclusion criteria 1

1. - Recurrent rectal cancer - Patients with a history of any arterial thrombotic event within the past 6 months, including angina (stable or unstable), MI, or CVA - Intolerance or contraindication to MR procedure - Patients with any other concurrent medical or psychiatric condition that are unstable or could jeopardize the safety of the patient and his/her compliance in the study - Gastro-intestinal abnormalities, inability to take oral medication, any condition affecting absorption - Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer. - Patients with a history of thrombotic episodes, such as deep venous thrombosis, pulmonary embolus, MI, or CVA occurring more than 6 months prior to enrollment may be considered for protocol participation, provided they are on stable doses of anticoagulant therapy. Patients who are anticoagulated for atrial fibrillation or other conditions may participate, provided they are on stable doses of anticoagulant therapy. - Patients receiving other anticancer or experimental therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. - Distant Relapse-Free Survival (DRFS) rate at 2.5 year - Association between 6-methylated gene panel and hazard ratio (HR) for relapse free survival - Association between ctDNA and relative hazard per standard deviation unit (HRσ) - Association between stromal score and odds ratio of response to treatment

Secondary endpoints 1

1. - Clinical complete response rate - Local recurrence and organ preservation rate, colostomy-free survival - Overall survival - Patient reported outcomes (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30 and its colorectal cancer specific module QLQ-38)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ASST Grande Ospedale Metropolitano Niguarda

Sponsor organisation

ASST Grande Ospedale Metropolitano Niguarda

Address

Piazza Dell'ospedale Maggiore 3

City

Milan

Postcode

20162

Country

Italy

Scientific contact point

Organisation

ASST Grande Ospedale Metropolitano Niguarda

Contact name

Salvatore Siena

Public contact point

Organisation

ASST Grande Ospedale Metropolitano Niguarda

Contact name

Salvatore Siena

Third parties 1

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications