A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum

Study Overview
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Brief Summary
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This is a multi-centre randomised trial comparing long course (LC) preoperative chemoradiation with short course (SC) preoperative radiotherapy for patients with localised T3 rectal cancer.

Detailed Description
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Objective: The objective is, in patients with T3 clinically resectable carcinoma of the rectum, to demonstrate that the local recurrence rate in patients treated with a long course (LC) of pre-operative radiotherapy with continuous infusion 5-FU is lower than that in patients treated with a short course (SC) of pre-operative radiotherapy with early surgery Eligibility Criteria: The main eligibility criteria are that the patient has clinically resectable adenocarcinoma of the rectum, a clinical stage T3 tumour whose lower border is within 12 cm of the anal verge, and no evidence of distant metastases. Endpoints: Primary endpoint is local recurrence. Secondary endpoints are overall survival, toxicity, abdminoperineal resection rate, quality of life. Treatment arms: SC arm: Radiotherapy (RT) 25 Gy in 5 fr in 1 week to be followed by surgery within 1 week and 6 cycles of postoperative chemotherapy 5FU/Folinic acid. LC arm: RT 50.4 Gy in 28 fr in 5½weeks with 5FU 225 mg/m2/day throughout the course of RT, to be followed by surgery 4-6 weeks after completion of RT. 4 cycles of adjuvant 5FU/Folinic acid will be given.

Official Title
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A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum

Conditions
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Adenocarcinoma of Rectum

Intervention / Treatment
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* Drug: Short Course Adjuvent Chemotherapy
* Drug: Long Course Adjuvant Chemotherapy
* Radiation: Short Course Radiotherapy
* Radiation: Long Course Radiotherapy
* Drug: Concurrent Chemotherapy
* Procedure: Initial Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All of the following must apply: Pathologically documented and clinically resectable adenocarcinoma of the rectum. The patient must be considered by the surgeon to be suitable for a curative resection. The patient must be considered by the radiation oncologist to have no contraindication to pre-operative radiotherapy. Clinical T3 stage tumour on endorectal ultrasound or MRI. When endorectal ultrasound cannot be performed satisfactorily due to a technical reason, such as stenosis or proximity of the tumour, and MRI is not available, infiltration of perirectal fat on CT scan is also acceptable. Tumour with lower border within 12 cm from anal verge on rigid sigmoidoscopy. ECOG performance status 0, 1 or 2. Adequate bone marrow function with neutrophil count at least 1.5 x 109/L and platelet count at least 100 x 109/L. Adequate liver function with bilirubin and alanine aminotransferase (ALT) <= 1.5 times the upper limit of normal. Adequate renal function with serum creatinine <= 1.5 times the upper limit of normal. Accessibility for treatment and follow-up. Written informed consent. Exclusion Criteria: None of the following must apply: Evidence of distant metastases. Recurrent rectal cancer. Unstable cardiac disease or clinically significant active infection. Other cancer in the last 5 years except treated non-melanoma skin cancer or carcinoma in situ of the cervix. Pregnant or lactating females or female patients of childbearing potential who have not been surgically sterilized or are without adequate contraceptive measures. Contraindication to insertion of a suitable indwelling venous catheter e.g. implantable central venous device (infuse-a-port), Hickman catheter or peripherally inserted central catheter. Prior pelvic or abdominal radiotherapy.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Short Course Radiotherapy<br>Short Course (SC) pre-operative radiotherapy, followed by surgery and adjuvant chemotherapy | Drug: Short Course Adjuvent Chemotherapy<br>* Post operative adjuvant chemotherapy: 5FU (425mg/m2) preceded by Folinic acid (20mg/m2) delivered over 5 days for 6 monthly cycles<br>Radiation: Short Course Radiotherapy<br>* 25 Gy in 5 fractions over 5 days.<br>* Other names: Short Course;|
| Active Comparator: Long Course Radiotherapy<br>Long Course (LC) radiotherapy delivered with concurrent chemotherapy, followed by surgery and adjuvant chemotherapy | Drug: Long Course Adjuvant Chemotherapy<br>* Post operative adjuvant 5FU (425mg/m2) preceded by folinic acid (20mg/m2) delivered over 5 days for 4 monthly cycles<br>Radiation: Long Course Radiotherapy<br>* 50.4 Gy delivered in 1.8 Gy fractions over 5 1/2 weeks.<br>* Other names: Long Course;Drug: Concurrent Chemotherapy<br>* 5FU 225mg/m2/day delivered IV over continous 7 day period for the duration of radiotherapy (5 1/2 weeks).<br>|
| Active Comparator: Surgery<br>Patients will receive initial surgery followed by post-operative management according to the NHMRC Guidelines for the prevention, early detection and management of colorectal cancer: Adjuvant therapy for rectal cancer. | Procedure: Initial Surgery<br>* Surgery is to be performed according to the NHMRC Guidelines for the prevention, early detection and management of colorectal cancer: Elective surgery for rectal cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local recurrence |  | Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) | 
| Toxicity |  | Interim analyses will occur annually. | 
| Abdominoperineal resection rate. This is defined as the proportion of all patients in any arm who undergo operation by abdominalperineal resection. |  | Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) | 
| Quality of life |  | Main analysis will occur at minimum 3 years follow up of all patients. (After 6 years since start of trial) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, radiotherapy, chemotherapy, chemoradiation, adjuvant therapy