Short-course Preoperative Chemoradiotherapy Followed by Delayed Operation for Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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Concurrent chemoradiotherapy (CRT) Radiotherapy 25 ㏉/5 fractions (start concomitantly at D1) ↓ ↓ ↓ ↓ ↓ Radical surgery 6 weeks after completion of chemoradiotherapy ↑ ↑ ↑ ↑ ↑ D1 - - - - - D5 5-Fluorouracil 400㎎/㎡/day + LV 20㎎/㎡/day IV bolus during the radiotherapy

Detailed Description
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Radiotherapy using tomotherapy is delivered in 5 Gy daily fractions for a total of 25 Gy in 5 fractions. A bolus injection of 5-fluorouracil (400 mg/m2/d)and leucovorin (20 mg/m2/d) is delivered concurrently on day 1-5 during radiotherapy. Total mesorectal excision is performed within 6±2 weeks. The pathological response of downstaing is the study endpoint.

Official Title
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Short-course Preoperative Chemoradiotherapy Followed by Delayed Operation for Locally Advanced Rectal Cancer: Phase II Multi-institutional Study

Conditions
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Rectal Cancer

Intervention / Treatment
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* Radiation: Radiation: short-course preoperative chemoradiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Pathologically proven diagnosis of adenocarcinoma of the rectum (located within 8㎝ above the anal verge) Locally advanced and curatively resectable tumor(cT3-4 classification) evaluated with magnetic resonance imaging(MRI) with or without transrectal ultrasonography(TRUS) Age ≥18 Performance Status(ECOG) 0-2 CBC/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows: Hemoglobin ≥ 10 g/dl, Absolute neutrophil count(ANC) ≥ 1,500 cells/㎣, Platelets ≥ 100,000cells/㎣ Metabolic panel within 14 days prior to registration on study, with adequate liver and renal function defined as follows: AST and ALT ≤ 60 IU/L, bilirubin ≤ 1.5 mg/dl, serum creatinine ≤ 1.5 mg/dl Patient must provide study-specific informed consent prior to study entry Exclusion Criteria : Any evidence of distant metastases(M1) Prior invasive malignancy (except non-melanomatous skin cancer and uterine cervical cancer in situ) unless disease free to a minimum of 3 years Hereditary rectal cancer; Familial adenomatous polyposis(FAP), Hereditary non-polyposis colorectal cancer(HNPCC), etc. Impending obstruction (except the case with colostomy) Severe, active comorbidity inappropriate to CRT as follows; Acute bacterial or fungal infection, transmural myocardial infarction within the last 6 months, unstable arrhythmia, angina and/or congestive heart failure, unstable arrhythmia Pregnancy or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception Unresected synchronous colon carcinoma Clinically unresectable rectal cancer

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: short-course CRT-5FU<br> | Radiation: Radiation: short-course preoperative chemoradiotherapy<br>* Drug: 5-Fluorouracil 5-Fluorouracil is administered intravenously at a dose of 400 mg/m2 once daily continuous regimen during RT(5 days). Radiation: Localization, simulation and immobilization Radiation dose and planning Total dose 25Gy, 5 fractions (5 Gy/day).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the pathologic response | downstaging(ypT0-2N0M0)rate | After surgery with pathology data | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor regression grade & MR volumetry | To evaluate the tumor regression grade & MR volumetry | After surgery with pathology data for TRG, at the pretreatment work-up and 1-4 days befor surgery | 
| Acute/ late toxicities | To evaluate the acute and late toxicities | preoperative CCRT to 3 months after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, short-course, chemoradiotherapy