Two-week Course Versus Conventionally Fractionated Chemoradiotherapy in Rectal Cancer

Study Overview
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Brief Summary
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The investigators compare two-week course of chemoradiation (33 Gy in 10 fractions with oral capecitabine) and conventional chemoradiation (50.4 Gy in 28 fractions with 5-FU and leucovorin) in this randomized trial.

Detailed Description
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1.1 experimental arm Two-week course concurrent chemoradiotherapy Radiotherapy, 33 Gy/10 fractions for 2 weeks ↓↓↓↓↓ ↓↓↓↓↓ Radical surgery 6 weeks after completion of chemoradiotherapy D1----------------------D12 Capecitabine 825 mg/m2, twice daily 1.2 control arm Standard concurrent chemoradiotherapy (CRT) Radiotherapy, 50.4 Gy/28 fractions for 6 weeks ↓↓↓↓↓ ↓↓↓↓↓ ↓↓↓↓↓ ↓↓↓↓↓ ↓↓↓↓↓ ↓↓↓ Radical surgery D1--------------------------------------------------------------------------D38 Bolus 5-FU, 400 mg/ m2 and leucovorin, 20 mg/ m2 during week 1 and 5 Capecitabine, 825 mg/ m2, bid

Official Title
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Two-Week COurse Versus Conventionally Fractionated Preoperative Chemoradiotherapy In Locally Advanced Rectal Cancer (TwoArc Trial): A Phase III Randomized Clinical Trial

Conditions
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Response to Toxin, Toxicity, Recurrence

Intervention / Treatment
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* Radiation: Two-week course of radiation
* Drug: Two-week course of radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed adenocarcinoma; distal margin of the tumor located < 10 cm from the anal verge; cT3-4N0-2 classification as determined by magnetic resonance imaging (MRI) and/or endorectal ultrasonography (EUS); no evidence of distant metastasis; Karnofsky performance score over 70; adequate bone marrow, liver, and renal function (leucocytes >4000/mm3, hemoglobin >10 g/dL, platelets >100,000/mm3; serum bilirubin <1.5 mg/dL, serum transaminase <2.5 times the upper normal limit; serum creatinine <1.5 mg/dL). Exclusion Criteria: Metastatic disease No complete resection of tumor (R2)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Experimental: Two-week course arm<br>Experimental arm receive 33 Gy in 10 fractions of radiation for 2 weeks with oral capecitabine. Two-week course of radiation, 33 Gy/10 fx and oral capecitabine, 825 mg/m2, bid | Radiation: Two-week course of radiation<br>* 33 Gy in 10 fractions for 2 weeks<br>* Other names: experimental arm;Drug: Two-week course of radiation<br>* oral capecitabine, 825mg/m2, bid<br>* Other names: experimental arm;|
| No Intervention: Conventional arm<br>conventionally fractionated radiation of 50.4 Gy/28 fx and 5-FU, 500 mg/m2 and leucovorin, 20 mg/m2 for 5 days, monthly or Capecitabine, 825 mg/m2, bid | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response from stage II-III to stage 0-I | Downstaging rate was evaluated by comparing pre-clinical and post-CRT pathological stages, and downstaging was defined as ypStage 0-I (ypT0-2N0M0) | from clinical staging time to radical surgery date (about 3 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity (acute and chronic) | During the course of radiotherapy, patients were evaluated weekly to assess acute toxicity. Patients were also followed 2 and 4 weeks after completion of radiotherapy and until 3 years after curative surgery to assess toxicity. Toxicity are assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0). | from radiation start to 3 years after radical surgery | 
| Recurrence and survival |  | 3-year recurrence-free survival and 3-year overall survival | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tumor response, toxicity, recurrence, chemoradiotherpy, rectum