Clinical trial NCT03001362: Patients With Rectal Cancer: a "Wait-and-see" Approach
Official title: Radical External Beam Chemoradiation in Patients With Rectal Cancer: a "Wait-and-see" Approach
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Colorectal Carcinoma
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2016-12-23
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Feasibility of a "wait and see" approach
timeFrame: One year
Secondary outcomes:
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: McGill University Health Centre- Cedars Cancer Centre
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Center-Cedars Cancer Centre
state: Quebec
Study officials:
affiliation: Radiation Oncologist
name: Neil Kopek, M.D.
role: PRINCIPAL_INVESTIGATOR
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