Pre-operative 3-DCRT vs IMRT for Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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The study aims to compare the incidence of acute grade 2 GI toxicity in the Control 3-D Conformal Radiotherapy compared to the Intensity Modulated Radiotherapy (IMRT) arm for locally advanced rectal cancer.

Detailed Description
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Pre-operative radiotherapy (RT) or chemo-radiotherapy (CRT) is internationally accepted as standard practice in the management of locally advanced rectal cancer. Multiple randomised trials have proved pre-operative CRT and RT, compared to surgery alone, reduce local recurrence, even prior to optimal surgery, and may improve survival for T3 circumferential resection margin (CRM) negative patients. This study aims to determine if 3-DCRT or IMRT result in lower incidence of grade 2 GI toxicities. Acute toxicities will be assessed weekly during radiotherapy, and at 2 and 4 week post treatment. Late toxicities will be assessed at 3, 6, 9, 12, 18, 24 months post treatment, and annually to 10 years.

Official Title
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Randomised Phase II Study of Pre-operative 3-D Conformal Radiotherapy (3-DCRT) Versus Intensity Modulated Radiotherapy (IMRT) for Locally Advanced Rectal Cancer

Conditions
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Locally Advanced Rectal Cancer

Intervention / Treatment
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* Radiation: IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing pre-operative pelvic chemo-radiotherapy for histologically confirmed rectal adenocarcinoma, with the following staging: cT3N0-2, cT4N0-2, cT(any)N1-2, cT(any)N(any) CRM at-risk [AJCC version V] Staging / imaging of pelvis with MRI, and CT Thorax/Abdomen No evidence of metastatic disease ECOG Performance Status 0 - 2 Age > or equal to 18 years Provision of written informed consent in line with ICH-GCP guidelines Exclusion Criteria: Previous radiotherapy to the pelvic region Patients in whom induction chemotherapy has been delivered prior to chemo- radiotherapy History of inflammatory bowel disease Previous hip replacement Previous bowel surgery (excluding procedures/operations which would not result in small bowel adhesions - at the discretion of the Principal Investigator) Patients with other syndromes/conditions associated with increased radiosensitivity Any other co-existing malignancies within the past 5 years other than non- melanoma skin cancer Pregnancy or lactation at the time of proposed randomisation Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study or if it is felt by the research / medical team that the patient may not be able to comply with the protocol

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 |
| --- | --- |
| Experimental: Experimental Arm<br>50.4 Gy / 28# external beam pelvic radiotherapy delivered using IMRT | Radiation: IMRT<br>* IMRT will be given to some patients to enable comparison of the acute grade 2 GI toxicities compared to those patients receiving their radiotherapy by 3-DCRT<br>|
| No Intervention: Control Arm<br>50.4 Gy / 28# external beam pelvic radiotherapy delivered using a 3-Dimensional (3-D) planned technique | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in incidence of grade 2 or higher GI toxicity | To determine if there is a reduction in the incidence of grade 2 or higher acute GI toxicity in the IMRT arm, as compared to the Control / 3-D arm, graded by the NCI-CTCAE Version 4 | 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare incidence of acute grade > 2 GU toxicity | To compare the incidence of acute grade > 2 GU toxicity in the IMRT arm, as compared to the Control / 3-D arm, graded by the NCI-CTCAE Version 4 | 10 years | 
| Evaluate incidence of late GI and GU toxicity | To evaluate the incidence of late GI and GU toxicity graded by the NCI-CTCAE Version 4 | 10 years | 
| Rate of loco-regional control | To estimate the rate of loco-regional control by assessing CT / MRI imaging / biopsy | 10 years | 
| Assess quality of life | To assess QoL according to the EORTC QLQ-C30 and EORTC QLQ-CR29 | 10 years | 
| Rate of disease free survival | To estimate the rate of disease-free survival | 10 years | 
| Estimate overall survival | To estimate the overall survival rate | 10 years | 
| Differences in the toxicity profile between the two types of neoadjuvant concomitant chemotherapy, graded by the NCI-CTCAE Version 4 | To compare the differences in the toxicity profile between the two types of neoadjuvant concomitant chemotherapy, graded by the NCI-CTCAE Version 4 | 10 years |