No Surgery Trial / Two Dose-escalation Strategies

Study Overview
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Brief Summary
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A randomized study of 145 patients. Patients with a clinical T2-3 N0 rectal cancer will be randomized to two arms (arm A: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy compared to arm B: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions).

Detailed Description
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It is becoming clear that there is a now an international consensus that rectal cancer research efforts need to be more focused in optimizing a non-surgical approach. This concept is very relevant to an ageing patient population with multiple co-morbidities regularly seen at the Jewish General Hospital and across the province. After interim analysis on 40 patients of the pilot study a phase III study is proposed. We are therefore proposing a phase III multicentric study of 145 patients to compare the two best known radiation dose escalation strategies and to achieve a complete clinical response. Patients with a clinical T2-3 N0-1 rectal cancer will be randomized to two arms (arm A: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy compared to arm B: standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions). Patients that have a high risk of recurrence or with more advanced stages of the disease will be excluded from the study, as only the local disease is being treated. The primary outcome for this proposal is rectum preservation in treated patients.

Official Title
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A Phase III Study Testing Two Dose Escalation Strategies to Increase the Population of Complete Responders After Radiation Therapy in the Context of Organ Preservation for Patients With Rectal Cancer

Conditions
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Stage II Rectal Cancer

Intervention / Treatment
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* Procedure: Complete responders and Non-complete responders
* Radiation: Chemoradiation + EBRT Boost
* Radiation: Chemoradiation + HDRBT Boost


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rectal cancer patients, clinically staged as T2-T3 by MRI or endoscopic/trans-rectal ultrasound Rectal cancer staged as N0 by MRI or EUS/TRUS No metastatic lesion Rectal tumor occupying less than half of the circumference Tumor less than 5 cm on its largest dimension Tumor located at less than 10 cm from the anal verge Tumor penetration less than 5 mm in the mesorectal fat Tumor accessible for brachytherapy Lumen accessible for colonoscopy Patient should be a suitable candidate for brachytherapy and chemotherapy Older than 18 years of age Adequate birth control measures in women of childbearing potential Written informed consent Exclusion Criteria: Patients with previous pelvic radiation Evidence of distant metastasis Extension of malignant disease to the anal canal Tumors staged as T4 Tumors larger than 5 cm in length

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: RCT
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemoradiation + EBRT Boost<br>standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy in 5; Complete responders and Non-complete responders | Procedure: Complete responders and Non-complete responders<br>* Patients that are complete responders will not have surgery. Patients that are non-complete responders will have surgery.<br>Radiation: Chemoradiation + EBRT Boost<br>* 45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and an external beam boost of 9 Gy in 5<br>|
| Experimental: Chemoradiation + HDRBT Boost<br>standard chemoradiation (45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions; Complete responders and Non-complete responders | Procedure: Complete responders and Non-complete responders<br>* Patients that are complete responders will not have surgery. Patients that are non-complete responders will have surgery.<br>Radiation: Chemoradiation + HDRBT Boost<br>* 45 Gy in 25 with concomitant 5-FU or Xeloda chemotherapy) and followed by a brachytherapy boost of 30 Gy in 3 fractions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TME-free survival | Time from date of randomization to either TME or death in the intention to treat population | 2 years post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Recurrence | Number of participants with Local recurrence as assessed by tests during follow-up visits. | 2 years post treatment | 
| Disease-free survival | The time between the date of randomization and recurrence, either in the pelvis or metastases. Patients without an event will be censored at the last date the patient was known to be disease-free. | 5 years post treatment | 
| Overall survival | The time between date of randomization and date of death due to any causes. | 5 years post treatment | 
| Overall Quality of life | Quality of life Questionnaires over different time point | 5 years post treatment |