Neoadjuvant ChemoradiotherapyTHUNDER2NCT04815694
THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI Guided Radiotherapy
A study testing RT Dose escalation in LARC patients with an Early Regression Index > 13.1 at second week on nCRT in people with Neoadjuvant Chemoradiotherapy and Locally Advanced Rectal Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoadjuvant Chemoradiotherapy, Locally Advanced Rectal Cancer, Pathological Complete Response
- What is being tested?
- RT Dose escalation in LARC patients with an Early Regression Index > 13.1 at second week on nCRT
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 179 participants
- Where
- 1 siteItaly
- Study dates
- 17 Mar 2021to Oct 2031
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione Policlinico Universitario A.Gemelli IRCCS
Roma, Roma, 00168
Margherita Zona, +39 0630156261, margherita.zona@policlinicogemelli.it
About this study
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.
Read more
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.
Read the detailed description
Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality for locally advanced rectal cancer (LARC). Patients who achieve a complete response (CR) after treatment generally experience improved local control, metastasis-free survival, and overall survival. Because response to radiotherapy is dose-dependent in rectal cancer, dose escalation may increase complete response rates. The ability to identify patients who are unlikely to achieve a complete response before surgery or during treatment is therefore of major clinical importance. An Early Tumor Regression Index (ERI) has been developed to predict pathological complete response after nCRT. Patients with ERI values below 13.1 have been shown to demonstrate a stronger response during treatment and a lower probability of developing distant relapse.
The primary aim of this clinical trial is to evaluate the impact of adaptive radiotherapy dose escalation in rectal cancer by identifying poor responders during treatment using ERI and increasing the prescribed radiation dose in these patients. Using this adaptive boosting strategy, an increase of approximately 10% in the complete response rate is expected. All enrolled patients receive chemoradiotherapy delivered using a 0.35 Tesla magnetic resonance-guided radiotherapy (MRgRT) system.
The radiotherapy schedule consists of 55 Gy in 25 fractions to the gross tumor volume and corresponding mesorectum, together with 45 Gy in 25 fractions to the whole pelvis. Concomitant chemotherapy consists of continuous oral capecitabine or 5-fluorouracil. Oxaliplatin may be added in patients considered at high risk of recurrence. Daily magnetic resonance imaging is performed throughout treatment. 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 treatment replanning with dose escalation up to 60.1 Gy to the residual tumor volume. For selected high-risk patients, consolidation chemotherapy with three cycles of the FOLFOX regimen may be administered during the interval before surgery. Patients achieving a complete clinical response may be managed using a Watch-and-Wait strategy according to multidisciplinary team evaluation.
Following protocol amendments, the study has been expanded to include additional patients for longitudinal multi-omics analyses. Stool samples are collected for gut microbiome characterization, including metagenomic, metabolomic, and metatranscriptomic analyses. Blood samples are collected for circulating tumor DNA (ctDNA) analyses and other blood-based biomarkers. These data are integrated with magnetic resonance imaging-derived delta-radiomics features to develop composite biomarker models aimed at improving prediction of treatment response and supporting personalized treatment strategies in locally advanced rectal cancer.
- Conditions
- Neoadjuvant Chemoradiotherapy, Locally Advanced Rectal Cancer, Pathological Complete Response
- Being tested
- RT Dose escalation in LARC patients with an Early Regression Index > 13.1 at second week on nCRT
- Keywords
- MRI guided radiotherapy, Early Regression Index- ERI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RT Dose escalation in LARC patients with an Early Regression Index > 13.1 at second week on nCRTRadiation
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 group | Role | What they receive |
|---|---|---|
| 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). Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response
ypT0N0 in case of TME, ypT0ycN0 in case of LE, ycT0N0 in case of WW
Measured: 6 months
Prospective validation of delta radiomics MR-guide Radiotherapy model
correlation between response prediction and clinical or pathological response
Measured: 6 months
Secondary outcomes (12)
3 years Local control
survival outcomes
Measured: 3 years follow up
3 years Metastasis Free Survival
survival outcomes
Measured: 3 years follow up
3 years Disease Free Survival
survival outcomes
Measured: 3 years follow up
3 years Overall Survival
survival outcomes
Measured: 3 years follow up
R0 resection rate
percentage of surgical intervention with negative margins
Measured: 6 months
Tumor Regression Grade 2
surgical outcomes
Measured: 6 months
Neoadjuvant rectal (NAR) score
surgical outcomes
Measured: 6 months
Tumor Regression Grade 1
surgical outcomes
Measured: 6 months
Sphincter preservation rate
percentage of surgical intervention without the positioning of permanent stomia
Measured: 6 months
Organ preservation rate
percentage of patients underwent conservative approaches (WW or EL)
Measured: 3 years follow up
Rectal function
impact of therapy on rectal functions by MSKCC questionnaire (from always to never with 5 items)
Measured: 3 years follow up
Sexual function
impact of therapy on sexual function by IIEF and FSFI questionnaires (from 1 worst to 5 better)
Measured: 3 years follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2021
- Study start17 Mar 2021
- Primary completionJan 2027 (estimated)
- Study completionOct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Neoadjuvant ChemoradiotherapyStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 179 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Viewray Inc.
- Responsible party
- Principal investigator, CHILOIRO GIUDITTA, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Investigators
- Giuditta Chiloiro, MD PhD, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04815694
- Sponsor's protocol ID
- 3460
- Acronym
- THUNDER2
- Status last verified
- Jul 2026
- First submitted
- 12 Mar 2021
- Last updated
- 10 Jul 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chiloiro G, Romano A, Boldrini L, de Giacomo F, Panza G, Bono F, Tran HE, Nardini M, Placidi L, Cusumano D, Menghi R, Barbaro F, Pecere S, Gambacorta MA. Early regression index-guided adaptive dose escalation in locally advanced rectal cancer: results of the prospective THUNDER-2 trial. Radiother Oncol. 2026 Aug 4;223:111719. doi: 10.1016/j.radonc.2026.111719. Online ahead of print.
PubMed 42551632Chiloiro 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.
PubMed 35033008
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI Guided Radiotherapy
- ClinicalTrials.gov ID
- NCT04815694
- Acronym / sponsor ID
- THUNDER2 / 3460
- Conditions
- Neoadjuvant Chemoradiotherapy, Locally Advanced Rectal Cancer, Pathological Complete Response
- Keywords
- MRI guided radiotherapy, Early Regression Index- ERI
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 179 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Collaborators
- Viewray Inc.
- Study start
- 17 Mar 2021 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Oct 2031 (estimated)
- First posted
- 25 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality for locally advanced rectal cancer (LARC). Patients who achieve a complete response (CR) after treatment generally experience improved local control, metastasis-free survival, and overall survival. Because response to radiotherapy is dose-dependent in rectal cancer, dose escalation may increase complete response rates. The ability to identify patients who are unlikely to achieve a complete response before surgery or during treatment is therefore of major clinical importance. An Early Tumor Regression Index (ERI) has been developed to predict pathological complete response after nCRT. Patients with ERI values below 13.1 have been shown to demonstrate a stronger response during treatment and a lower probability of developing distant relapse.
The primary aim of this clinical trial is to evaluate the impact of adaptive radiotherapy dose escalation in rectal cancer by identifying poor responders during treatment using ERI and increasing the prescribed radiation dose in these patients. Using this adaptive boosting strategy, an increase of approximately 10% in the complete response rate is expected. All enrolled patients receive chemoradiotherapy delivered using a 0.35 Tesla magnetic resonance-guided radiotherapy (MRgRT) system.
The radiotherapy schedule consists of 55 Gy in 25 fractions to the gross tumor volume and corresponding mesorectum, together with 45 Gy in 25 fractions to the whole pelvis. Concomitant chemotherapy consists of continuous oral capecitabine or 5-fluorouracil. Oxaliplatin may be added in patients considered at high risk of recurrence. Daily magnetic resonance imaging is performed throughout treatment. 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 treatment replanning with dose escalation up to 60.1 Gy to the residual tumor volume. For selected high-risk patients, consolidation chemotherapy with three cycles of the FOLFOX regimen may be administered during the interval before surgery. Patients achieving a complete clinical response may be managed using a Watch-and-Wait strategy according to multidisciplinary team evaluation.
Following protocol amendments, the study has been expanded to include additional patients for longitudinal multi-omics analyses. Stool samples are collected for gut microbiome characterization, including metagenomic, metabolomic, and metatranscriptomic analyses. Blood samples are collected for circulating tumor DNA (ctDNA) analyses and other blood-based biomarkers. These data are integrated with magnetic resonance imaging-derived delta-radiomics features to develop composite biomarker models aimed at improving prediction of treatment response and supporting personalized treatment strategies in locally advanced rectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| LARC patients treated by MRgRT with Early Regression Index (ERI) at 10th fraction >13.1 | Experimental | Radiation: RT Dose escalation in LARC patients with an Early Regression Index > 13.1 at second week on nCRTAll 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). |
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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;
Key exclusion criteria (12 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RT Dose escalation in LARC patients with an Early Regression Index > 13.1 at second week on nCRTThe 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. | Radiation | LARC patients treated by MRgRT with Early Regression Index (ERI) at 10th fraction >13.1 |
Primary outcome
Complete response
Time frame: 6 months
ypT0N0 in case of TME, ypT0ycN0 in case of LE, ycT0N0 in case of WW
Prospective validation of delta radiomics MR-guide Radiotherapy model
Time frame: 6 months
correlation between response prediction and clinical or pathological response
12 secondary outcomes
3 years Local control
Time frame: 3 years follow up
3 years Metastasis Free Survival
Time frame: 3 years follow up
3 years Disease Free Survival
Time frame: 3 years follow up
3 years Overall Survival
Time frame: 3 years follow up
R0 resection rate
Time frame: 6 months
Tumor Regression Grade 2
Time frame: 6 months
Neoadjuvant rectal (NAR) score
Time frame: 6 months
Tumor Regression Grade 1
Time frame: 6 months
Sphincter preservation rate
Time frame: 6 months
Organ preservation rate
Time frame: 3 years follow up
Rectal function
Time frame: 3 years follow up
Sexual function
Time frame: 3 years follow up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2026.
- Derived from this study: PubMed 42551632Chiloiro G, Romano A, Boldrini L, de Giacomo F, Panza G, Bono F, Tran HE, Nardini M, Placidi L, Cusumano D, Menghi R, Barbaro F, Pecere S, Gambacorta MA. Early regression index-guided adaptive dose escalation in locally advanced rectal cancer: results of the prospective THUNDER-2 trial. Radiother Oncol. 2026 Aug 4;223:111719. doi: 10.1016/j.radonc.2026.111719. Online ahead of print.
- Derived from this study: PubMed 35033008Chiloiro 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Giuditta Chiloiro, MD PhD principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing RT Dose escalation in LARC patients with an Early Regression Index > 13.1 at second week on nCRT in people with Neoadjuvant Chemoradiotherapy and Locally Advanced Rectal Cancer, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Giuditta Chiloiro, MD PhD (+ 39 3934360389, giuditta.chiloiro@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04815694, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2026.