Total Neoadjuvant Treatment Combined With Adaptive Radiotherapy for Rectal Cancer

Study Overview
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Brief Summary
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Diarrhea was the most frequently reported severe adverse event in the treatment regime of pre-operative sequential short-course radiotherapy followed by chemotherapy (so called total neo-adjuvant treatment). This study therefore investigates the benefit of on-couch adaptation for locally advanced rectal cancer patients undergoing this treatment regime.

Detailed Description
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This is a prospective single-arm study investigating the benefit of on-couch adaptation for locally advanced rectal cancer patients prescribed with pre-operative sequential short-course radiotherapy (RT) followed by Oxaliplatin-combined chemotherapy (mFOLFOX(6) or CAPOX). On-couch adaptation, where the radiation dose is tailored to the anatomy of the patient at each radiotherapy session. Firstly, the study will investigate if on-couch adaptation result in less gastro-intestinal adverse events, secondly it will reveal if this possible reduction lead to more patients being able to fulfill all cycles of prescribed chemotherapy.

Official Title
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TNT-RECORD:Total Neoadjuvant Treatment in Rectal Cancer With On-couch Adaptive Radiotherapy

Conditions
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Rectal Cancer

Intervention / Treatment
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* Radiation: On-couch adaptive radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with loco-regional advanced rectal adenocarcinoma with clinical indications for short-course with TNT chemotherapy i.e. having at least one of the following T4a, CRM+ (≤1 mm), N1c, N2 or extramural vascular invasion (EMVI+). Patients presenting at least one of these criteria in addition to involvement of the pelvic sidewall lymph nodes (PSW) can optionally be considered. ECOG status ≤ 1 Being willing and able to give full written consent for participation Exclusion Criteria: Previous rectal cancer treatment Previous irradiation to the treatment area e.g. prostate cancer Hip prosthesis Contraindications to MRI Pregnancy Abnormal DPYD genotype Known contraindication to 5-FU, Capecitabine or Oxaliplatin as judged by the investigators

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Intervention: daily on-couch adaptive radiotherapy | Radiation: On-couch adaptive radiotherapy<br>* A new treatment plan, guided by volumetric images, is created at each treatment session<br>* Other names: online ART;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of acute gastro-intestinal toxicity equal or higher than grade 2 | Incidence of acute gastro-intestinal toxicity from therapy graded according to CTCAE ver. 5. | Up to administration of the last course of chemotherapy or week 22, whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants that require alteration of chemotherapy due to toxicity | Alterations of chemotherapy, defined as dose-reduction or pre-maturely stopping chemotherapy administration | From treatment week 3 up to week 20 | 
| Number of patients with disease related treatment failure | Disease-related treatment failure include the first of any of the following events: (i) During treatment: Non-radical resection of primary tumor (R2 resection) or un-fit of for surgery due to progression, death from treatment (ii) During, or after treatment: Loco-regional recurrence (including regrowth after potential watch-and-wait), distant metastasis (including M re-staging at surgery), death from rectal cancer, second primary rectal cancer. | 5 years after surgery | 
| Number of patients with pathological complete response (pCR) | pCR after completion of the intended or tolerated TNT | At surgery i.e. in treatment week 23-28 | 
| Tumour regression grade | Radiological based clinical response evaluation on MR (mrTRG) | Baseline to response evaluation on MR in up to week 25 of the study | 
| Overall survival | Overall survival from time of inclusion until death | Follow-up until 5 years or death | 
| Incidence of late gastro-intestinal toxicity equal or higher than grade 2 | Incidence of late gastro-intestinal events (e.g.diarrhea, rectal hemorrhage, rectal and/or abdominal pain) from therapy graded according to CTCAE ver. 5. | 5 years |