Simultaneous Integrated Boost Preoperative Radiotherapy for Rectum Cancer

Study Overview
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Brief Summary
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The investigators propose a randomized non-inferiority trial that compares preoperative Fluoro Uracil (FU)-based chemoradiotherapy to radiotherapy with a simultaneous integrated boost. In patients with T3-4 rectal cancer, the latter approach is considered preferential with regard to toxicity and cost. The metabolic response of the tumor, as assessed by 18F-2-Fluoro-2-Deoxyglucose-Positron Emission tomography (18F-FDG PET) or PET-CT, will be used as a surrogate marker of cause specific outcome

Official Title
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Randomized Trial of Preoperative Radiotherapy With an Integrated Simultaneous Boost Compared to Chemoradiotherapy for T3-4 Rectal Cancer

Conditions
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Rectal Cancer

Intervention / Treatment
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* Other: Chemoradiotherapy
* Radiation: Radiotherapy with boost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histopathologically confirmed rectal adenocarcinoma with an inferior border within 15 cm of the anal verge the tumor has to have evidence of T3 or T4 disease on Magnetic Resonance Imaging (MRI) or endoluminal ultrasound Exclusion Criteria: unresectable metastatic disease Eastern Cooperative Oncology Group (ECOG) performance status > 3 patients not deemed fit for radiotherapy, capecitabine or surgery pregnant or lactating patients women with child bearing potential who lack effective contraception patients below 18 years old

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Concomitant chemoradiotherapy<br>Radiotherapy (23 x 2 Gy) + capecitabine 825mg/m2 p.o. twice daily, excluding weekends | Other: Chemoradiotherapy<br>* Radiotherapy (23 x 2 Gy) + capecitabine 825mg/m2 p.o. twice daily, excluding weekends<br>* Other names: Xeloda (capecitabine);|
| Experimental: Radiotherapy with boost<br>Radiotherapy (23 x 2 Gy), with a simultaneous integrated boost up to 55.2 Gy on the primary tumor | Radiation: Radiotherapy with boost<br>* Radiotherapy (23 x 2 Gy), with a simultaneous integrated boost up to 55.2 Gy on the primary tumor<br>* Other names: Preoperative radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| reduction in metabolic tumor activity |  | at baseline and at 5 to 6 weeks after neo-adjuvant therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| histological downgrading (Dworak classification) | pathological evaluation of surgical resection specimens | after the rectum surgery | 
| number of R0, R1 and R2 resections | pathological evaluation of surgical resection specimens | after the rectum surgery | 
| acute and late toxicity, according to the National Cancer Institute (NCI) - Common Terminology Criteria for Adverse Events v3.0 (CTCAE) |  | at baseline, every 6 months after completion of radiotherapy and then yearly until 3 years | 
| local control |  | every 6 months in the first year after completion of radiotherapy and then yearly until 3 years | 
| progression free survival |  | every 6 months in the first year after completion of radiotherapy and then yearly until 3 years | 
| survival | overall survival | every 6 months in the first year after completion of radiotherapy and then yearly until 3 years | 
| quality of life |  | at baseline, every 6 months in the first year after completion of radiotherapy and then yearly until 3 years | 
| cost evaluation |  | during the treatment and follow-ups | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal cancer, colorectal neoplasms, radiotherapy, chemoradiotherapy, T3-4 rectal cancer