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

NCT04815694 | Unknown

• 1 other identifier: 3460
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC) and patients achieving complete response to treatment (CR) usually have a better prognosis in terms of local control (LC), metastases-free survival (MFS) and overall survival (OS). Recently, an early tumour regression index (ERITCP) was introduced, to predict pathological CR (pCR) after nCRT in LARC patients. In particular, the authors found that the patients with ERITCP \<13.1 show a strong response during therapy and have a lower probability to experience distant relapses. Aim of this clinical trial is to investigate the impact of dose escalation in rectal cancer, identifying the poor responder cases using the ERI index during the course of radiotherapy and increasing the prescribed dose in these patients. Adopting this boosting protocol, an increase of 10% of CR (clinical and pathological) rate is expected. For patients enrolled in the trial, chemoradiotherapy (CRT) will be administered using the MRI guided Radiotherapy (MRgRT) machine available in our institution. If ERI will be inferior than 13.1 the patient will continue the original treatment. Patients with complete clinical response will go through wait and see approach. 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. The number of cases to be enrolled will be 63. The primary endpoints will be complete response considered as: ypT0N0 in case of Total Mesorectal Excision (TME), ypT0ycN0 in case of LE, ycT0N0 in case of WW; prospective validation of delta radiomics MR-guide Radiotherapy model.

Conditions

Neoadjuvant Chemoradiotherapy; Locally Advanced Rectal Cancer; Pathological Complete Response

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 cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0
• 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
• Eastern Cooperative Oncology Group (ECOG) 0-1
• Age over 18 years
• Adequate hematological function: granulocyte count \> 1500/microl; Hemoglobin level \> 10 g/dl; Platelet count \> 100000/microl; Alanine Aminotransferase/ aspartate aminotransferase (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;

Sponsors & Collaborators

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

Study Sites (1)

Fondazione Policlinico Universitario A.Gemelli IRCCS

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 A. 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: March 30, 2022
• Study Completion: September 30, 2022
• Last Updated: March 25, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)