Preoperative, Adaptive Radiotherapy Concomitant to Chemotherapy for Rectal Adenocarcinoma (Adaptive Rectal Cancer Trial 02)

NCT07580027 | Not Yet Recruiting DMC

• 1 other identifier: AdaptiveRectalCancer02
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this clinical study is to increase the rate of pathological responses up to 70% by means of improved patient selection operated by a radiobiological index called ERI\_TCP and by an increase in the dose of radiotherapy in the final concomitant boost of preoperative radiochemotherapy treatment for rectal adenocarcinoma.

Conditions

Locally Advanced Rectal Carcinoma

Keywords

adaptive radiotherapy; preoperative radiotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate

  Change the rate of pathological complete responses (pCR) from the present 41% to 70% in the population of patients with ERITCP\<32.6.

  The time between the end of radiochemotherapy and the availability of the histological examination, on which the complete pathological response is defined, is expected to be 8-10 weeks

Study Arms (1)

A single arm of patients will be treated

EXPERIMENTAL

A single arm of patients with locally advanced rectal cancer will be treated with preoperative radiochemotherapy.

Radiation: Preoperative, adaptive radiotherapy

Interventions

Preoperative, adaptive radiotherapy RADIATION

Preoperative radiotherapy will consist of 18 fractions to the mesorectum and regional lymph nodes. Halfway through the radiotherapy treatment, patients will undergo a second simulation MRI scan, from which a radiomic index called ERI\_TCP will be calculated: ERI\_TCP=-ln\[(1-(Vmid/Vpre)\]Vpre where Vpre is the volume of the rectal tumor pre-therapy, Vmid is the volume of the residual tumor still visible in the MR images intermediate to RT. This index is able to discriminate patients with a good probability of pathologic complete response (ERI\_TCP\<32.6) and exclude patients with zero probability of pathologic complete response (ERI\_TCP\>32.6). Patients with a good probability of response (41% in our experience) will receive a simultaneous boost delivered in the last 6 fractions to the residual tumor still visible in the intermediate MRI images (adaptive RT). Concomitant chemotherapy consists of Oxaliplatin 85 mg/m2 delivered on days -14, 0, +14, and Capecitabine 825 mg/m2 twice daily or les

A single arm of patients will be treated

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Initial phase (standard phase). These criteria represent the conditions for which preoperative chemoradiotherapy treatment for rectal cancer is clinically indicated
• Histologically confirmed rectal adenocarcinoma
• Microsatellite status: stable
• Stage T2N0 if lower rectal lesions are candidates for subsequent intersphincteric resection or abdominoperineal amputation with permanent colostomy
• Stage T3-T4N0 or any T with positive lymph nodes
• Lower margin of lesion no more than 12 cm from anal verge Adaptive radiotherapy phase (experimental phase)
• ERI\_TCP \< 32.6 calculated as follows: ERITCP=-ln\[(1-(Vmid/Vpre)\]Vpre where Vpre is the volume of the rectal tumor pre-therapy, Vmid is the volume of the residual tumor still visible in the images of the MR intermediate to RT)
• Lower margin of rectal lesion at least 1 cm from surgical resection line on images of the intermediate smc MRI
• ECOG (Eastern Cooperative Oncology Group) Performance Status ≤ 2
• Age: 18-80 years
• Written informed consent

You may not qualify if:

• Distant metastases
• Previous cancer excluding non-melanoma skin cancer diagnosed less than 5 years before rectal cancer appearance
• Previous chemotherapy or radiotherapy to the pelvis
• Contraindications to radiotherapy: active ulcerative colitis
• Contraindications to chemotherapy: NE\<1.5x10/L, Plt \< 100x10/L), creatinine \>1,5mg/dl, bilirubin \> 2mg/dl, AST/ALT \> 3x normal upper limit, significant cardiac disease, peripheral neuropathy.
• Pregnancy
• Breastfeeding

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

I.R.C.C.S. San Raffaele Hospital

Milan, 20132, Italy

Location

Related Publications (20)

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• Maggiulli E, Fiorino C, Passoni P, Broggi S, Gianolini S, Salvetti C, Slim N, Di Muzio NG, Calandrino R. Characterisation of rectal motion during neo-adjuvant radiochemotherapy for rectal cancer with image-guided tomotherapy: implications for adaptive dose escalation strategies. Acta Oncol. 2012 Mar;51(3):318-24. doi: 10.3109/0284186X.2012.666358.

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• Fiorino C, Gumina C, Passoni P, Palmisano A, Broggi S, Cattaneo GM, Di Chiara A, Esposito A, Mori M, Raso R, Ronzoni M, Rosati R, Slim N, De Cobelli F, Calandrino R, Di Muzio NG. A TCP-based early regression index predicts the pathological response in neo-adjuvant radio-chemotherapy of rectal cancer. Radiother Oncol. 2018 Sep;128(3):564-568. doi: 10.1016/j.radonc.2018.06.019. Epub 2018 Jun 29.

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• Fiorino C, Passoni P, Palmisano A, Gumina C, Cattaneo GM, Broggi S, Di Chiara A, Esposito A, Mori M, Ronzoni M, Rosati R, Slim N, De Cobelli F, Calandrino R, Di Muzio NG. Accurate outcome prediction after neo-adjuvant radio-chemotherapy for rectal cancer based on a TCP-based early regression index. Clin Transl Radiat Oncol. 2019 Jul 3;19:12-16. doi: 10.1016/j.ctro.2019.07.001. eCollection 2019 Nov.

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• 19) Purrello Giorgio, Spanu Dario, Passoni Paolo et al: Adaptive RT concomitant to oxaliplatin based chemoterapy as preoperative treatment for rectal cancer. Radiother Oncol 2024;194, suppl1 https://user-swndwmf.cld.bz/ESTRO-2024-Abstract-Book/1548/

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  BACKGROUND

Related Links

• Related Info

Study Officials

• Nadia Di Muzio, Professor

  Radiation Oncology Department

  STUDY DIRECTOR

Central Study Contacts

Paolo Passoni, Doctor

CONTACT

+39 02 26437643; passoni.paolo@hsr.it

Miriam Torrisi, Doctor

CONTACT

+39 02 26438146; torrisi.miriam@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Model Details: The aim of this clinical study is to increase the rate of pathological responses up to 70% by means of improved patient selection operated by a radiobiological index called ERI\_TCP and by an increase in the dose of radiotherapy in the final concomitant boost of preoperative radiochemotherapy treatment for rectal adenocarcinoma.

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: May 12, 2026
• Study Start: April 30, 2026
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: May 12, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Individual participant data will be shared for the duration of the study up to 1 year upon request to the principal investigator and approval by our ethics committee.
• Access Criteria: Individual participant data will be made available to all researchers who will request it from the principal investigator and approved by our ethics committee

Locations

IT (1)