Patients With Rectal Cancer: a Wait-and-see Approach

Study Overview
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Brief Summary
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Patients with histologically proven adenocarcinoma of the rectum will receive pelvic radiotherapy to a dose of 45Gy in 25 fractions with a tumor boost to a dose of 9Gy in 5 fractions (thus total of 54Gy/30Fx to the primary tumor), combined with radio sensitizing chemotherapy. Patients will then be closely monitored, through endoscopy and imaging, for response to treatment and relapse. Salvage oncologic surgery to be offered if there is failure to achieve complete clinical response or in the event of a loco regional relapse.

Detailed Description
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The combination of preoperative (chemo)radiotherapy and total mesorectal excision (TME) has been shown to reduce the risk of local recurrence in patients with resectable adenocarcinoma of the rectum. The improved local control rates come at the price of an increased risk of surgical complications, including a postoperative death rate of 2-8 percent which may reach 30 per cent at 6 months in those aged over 85 years, as well as long-term impact on anorectal, urinary and sexual function. Patients with cancers in the low rectum in close proximity to the sphincter muscles, may require a permanent stoma, which can be associated with high psychological morbidity. Preoperative chemoradiotherapy followed by a delay to resection can produce pathological complete responses. One review of phase II and III studies identified an overall pCR rate of 13.5%, but even higher rates of pCR have been observed with doses of radiotherapy exceeding 45 Gy . Certainly patients who proceed to radical surgery after achieving a pCR with chemo radiation do have favorable long-term outcomes. But do patients whose tumor has already been sterilized by chemo radiotherapy need to proceed with radical surgery? A number of studies have now emerged highlighting the rationale of a 'wait and see' policy for patients who achieve a complete clinical response (cCR) after chemo radiotherapy. The majority of the clinical data supporting this approach have come from Brazil. The Brazilian data suggests that observation of such patients yields survival rates similar to those of patients who undergo radical surgery with confirmation of pCR. More recent studies from the United Kingdom and the Netherlands appear to support the feasibility of this approach. To date there is no published prospectively collected data of a wait-and-see policy from a North American Centre.

Official Title
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Radical External Beam Chemoradiation in Patients With Rectal Cancer: a Wait-and-see Approach

Conditions
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Colorectal Carcinoma

Intervention / Treatment
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* Radiation: Radical external beam radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pelvic MRI defined disease (at least one of the following): mesorectum involved or breached - includes involvement of adjacent organ (s) (T3-T4) involvement of muscularis propria (T2) extra-mural vascular invasion tumour deposit within the mesorectum one or more involved mesorectal lymph node Patients are considered medically fit for oncologic resection ECOG performance status 0 or 1 No evidence of established metastatic disease (CT chest and abdomen) Absolute neutrophil count >1.5x109/L; platelets >100x109/L, Serum transaminase <3 x ULN; Adequate renal function (Cockroft Gault estimation >50 mL/min) Bilirubin <1.5 x ULN Ability to comply with oral medication Willingness and ability to give informed consent and comply with treatment and follow up schedule Age 18 or over Exclusion Criteria: Previous radiotherapy to the pelvis (including brachytherapy) Enlarged extramesorectal nodes Uncontrolled cardiorespiratory comorbidity (includes patients with inadequately controlled angina or myocardial infarction within 6 months of randomisation) T1N0 disease without extra-mural venous invasion Unequivocal evidence of metastatic disease (includes resectable metastases) Major impairment of bowel function without defunctioning stoma/ileostomy (baseline grade 3 diarrhoea or clinically significant faecal incontinence) History of another malignancy within the last 5 years except successfully treated basal cell cancer of skin or carcinoma in situ of uterine cervix. Known dihydropyrimidine dehydrogenase deficiency Known Gilberts disease (hyperbilirubinaemia) Taking warfarin or phenytoin or sorivudine Gastrointestinal disorder which would interfere with oral therapy and its bioavailability Pregnant, lactating, or pre-menopausal women not using adequate contraception Unfit to receive any study treatment or subsequent surgical resection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Radical External Beam RT for Colorectal Ca<br>A single arm consisting of: Radical external beam RT dose of 54 Gy in 30fx with radiosensitizing chemotherapy as per institutional standard | Radiation: Radical external beam radiotherapy<br>* pelvic radiotherapy to a dose of 45 Gy in 25 fractions with a tumor boost to a dose of 9 Gy in 5 fractions (thus total of 54 Gy/30 fractions to the primary tumor), combined with radio sensitizing chemotherapy.<br>* Other names: Radiosensitizing chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of a wait and see approach | Rate of failure to achieve CR or the rate of recurrence after achieving CR | One year |