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RECRUITING

NCT04815694

THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI Guided Radiotherapy

Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

View on ClinicalTrials.gov

Summary

Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality for locally advanced rectal cancer (LARC), and patients achieving complete response (CR) generally have improved local control, metastasis-free survival, and overall survival. The aim of this clinical trial is to investigate the impact of radiotherapy dose escalation in rectal cancer by identifying poor responders during treatment using the Early Tumor Regression Index (ERI). Patients are treated using magnetic resonance-guided radiotherapy (MRgRT). ERI is calculated at fraction 10. Patients with an ERI value below 13.1 continue the standard treatment schedule, whereas patients with an ERI value above 13.1 undergo adaptive replanning with dose escalation up to 60.1 Gy to the residual tumor volume. Concomitant chemotherapy consists of fluoropyrimidine-based treatment, with oxaliplatin permitted in patients at high risk of recurrence. In selected high-risk patients, consolidation chemotherapy with three cycles of FOLFOX may be administered during the interval before surgery. Following protocol amendments, the study was expanded to include a total planned enrollment of 179 patients. Additional blood samples for circulating tumor DNA (ctDNA) analysis and stool samples for gut microbiome profiling are collected at predefined time points. These longitudinal multi-omics data are integrated with magnetic resonance imaging-based delta-radiomics features to develop composite biomarker models for prediction of treatment response. The primary outcome measures are complete response, defined as ypT0N0 after Total Mesorectal Excision (TME), ypT0 ycN0 after Local Excision (LE), or ycT0N0 in patients managed with Watch and Wait, and the prospective validation of the magnetic resonance-guided radiotherapy delta-radiomics predictive model.

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

179

Start Date

2021-03-17

Completion Date

2031-10

Last Updated

2026-07-10

Healthy Volunteers

Conditions

Neoadjuvant Chemoradiotherapy Locally Advanced Rectal Cancer Pathological Complete Response

Interventions

RADIATION

RT Dose escalation in LARC patients with an Early Regression Index > 13.1 at second week on nCRT

The initial radiotherapy treatment will consist in delivering 55 Gy in 25 fractions on GTV plus the corresponding mesorectum of 45Gy in 25 fractions on the whole pelvis. Chemotherapy with 5-fluorouracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla Magnetic resonance image will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated. If ERI will be inferior than 13.1 the patient will continue the original treatment. If ERI will be higher than 13.1 the treatment plan will be reoptimized considering the residual tumor at fraction 10 as new therapy volume, where the dose will be intensified to reach 60.1 Gy.

Inclusion Criteria: * Histological proven adenocarcinoma of the rectum; * cT2-4, or cN0-2 (also extramesorectal nodes), or mesorectal fascia involvement for tumor (MRF+) or extramural venous invasion (EMVI+); * cM0; * No prior radiotherapy in pelvic region; * Tumour located between 0 and 15 cm above the anal verge; * Not mesorectal fascia involvement for tumor; * No extramesorectal nodes involvement; * No extramural venous invasion (EMVI); * No rectal mucinous adenocarcinoma histology; * No contra-indications for MRI; * ECOG 0-1; * Age over 18 years; * Adequate hematological function: granulocyte count \> 1500/microl, Hemoglobin level \> 10 g/dl, Platelet count \> 100000/microl, ALT/AST: 7-45 UI/L; * No other malignancies in the previous history (except skin and initial cervical cancer); * Absence of important comorbidities: severe cardiac or coagulative disease, moderate or severe restrictive/obstructive lung deficit, severe cognitive impairment, moderate and severe renal and hepatic impairment; * Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial; * Absence of pregnancy or lactating female patients; * Written informed consent. Exclusion Criteria: * Distant metastases (cM1); * Prior radiotherapy in the pelvic region; * Tumour located lower than 0 cm or higher than 15 cm above the anal verge; * Rectal mucinous adenocarcinoma histology; * Contra-indications for Magnetic Resonance Imaging (MRI); * Eastern Cooperative Oncology Group (ECOG) performance status score \>= 2; * Age under 18 years; * Inadequate hematological function (Granulocyte count \<= 1500/microl, Hemoglobin level \<= 10 g/dl, Platelet count \<= 100000/microl, ALT/AST outside 7-45 UI/L); * History of other malignancies (except skin cancer and initial cervical cancer); * Presence of severe comorbidities (severe cardiac or coagulative disease, moderate or severe restrictive/obstructive lung deficit, severe cognitive impairment, moderate/severe renal or hepatic impairment); * Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; * Pregnant or lactating female patients.

Locations (1)

Fondazione Policlinico Universitario A.Gemelli IRCCS

Roma, Roma, Italy