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

NCT04815694 | Recruiting

• 1 other identifier: 3460
• Study Type: interventional
• Target: 179
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Locally Advanced Rectal Cancer; Pathological Complete Response; Neoadjuvant Chemoradiotherapy

Keywords

MRI guided radiotherapy; Early Regression Index- ERI

Outcome Measures

Primary Outcomes (2)

• Complete response

  ypT0N0 in case of TME, ypT0ycN0 in case of LE, ycT0N0 in case of WW

  6 months

• Prospective validation of delta radiomics MR-guide Radiotherapy model

  correlation between response prediction and clinical or pathological response

  6 months

Secondary Outcomes (12)

• 3 years Local control

  3 years follow up

• 3 years Metastasis Free Survival

  3 years follow up

• 3 years Disease Free Survival

  3 years follow up

• 3 years Overall Survival

  3 years follow up

• R0 resection rate

  6 months

Study Arms (2)

LARC patients treated by MRgRT with Early Regression Index (ERI) at 10th fraction >13.1

EXPERIMENTAL

All patients will be treated on MRgRT, at the second week , patients with an ERI \> 13.1 will underwent RT dose intensification on GTV + 3 mm to 60.1 Gy with a Simultaneous Integrated Boost (SIB).

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

LARC patients treated by MRgRT with Early Regression Index (ERI) at 10th fraction < 13.1

NO INTERVENTION

All patients will be treated on MRgRT, at the second week , patients with an ERI \< 13.1 will underwent standard RT dose of 55Gy on tumor and corresponding mesorectum

Interventions

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

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.

LARC patients treated by MRgRT with Early Regression Index (ERI) at 10th fraction >13.1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead
• Viewray Inc.: collaborator

Study Sites (1)

Fondazione Policlinico Universitario A.Gemelli IRCCS

Roma, Roma, 00168, Italy

RECRUITING

Related Publications (1)

• Chiloiro G, Cusumano D, Boldrini L, Romano A, Placidi L, Nardini M, Meldolesi E, Barbaro B, Coco C, Crucitti A, Persiani R, Petruzziello L, Ricci R, Salvatore L, Sofo L, Alfieri S, Manfredi R, Valentini V, Gambacorta MA. THUNDER 2: THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy. BMC Cancer. 2022 Jan 15;22(1):67. doi: 10.1186/s12885-021-09158-9.

  PMID: 35033008 DERIVED

Study Officials

• Giuditta Chiloiro, MD PhD

  Fondazione Policlinico Universitario Agostino Gemelli IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuditta Chiloiro, MD PhD

CONTACT

+ 39 3934360389; giuditta.chiloiro@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Medical Doctor PhD

Model Details: 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.

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: March 25, 2021
• Study Start: March 17, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): October 1, 2031
• Last Updated: July 10, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)