Official Title
Phase II Study to Assess the Safety of Non-operative Management for Low Rectal Cancer
Summary:
This is a 5 year Phase II study to evaluate the safety of non-operative management (NOM) in
patients with low rectal cancer (LRC) who achieve a complete clinical response (cCR)
following chemoradiotherapy (CRT). The safety of NOM will be evaluated by assessing (i) rate
of local re-growth and (ii) rate of macroscopically positive resection margin (R2) when
surgery is required due to local re-growth. NOM will be considered safe or as effective as
surgery to achieve local control if the rate of local re-growth is equal to or less than 30%
and the rate of a macroscopically positive margin is 0%.
Trial Description
Primary Outcome:
- Rate of local re-growth
- Rate of macroscopically positive resection margin
Secondary Outcome:
- Rate of overall survival
- Rate of disease-free survival
- Colostomy-free survival
- Quality of Life
- Bowel Function
Background: The standard treatment for low rectal cancer (LRC) involving the anal sphincter
involves combined, pre-operative chemotherapy and radiation therapy (CRT) followed by surgery.
Surgery involves removal of the rectum and anus and creation of a permanent colostomy and has
significant long term effects on bowel and sexual function and body image. Because of the
high morbidity of surgery, there has been increasing interest in non-operative management
(NOM) for LRC. The NOM approach involves deferral of surgery and active surveillance of all
patients with LRC who have achieved a complete clinical response (i.e., have no residual
tumour) following completion CRT which occurs in approximately 30% of patients. To date,
while there have been a few, prospective single institution studies that have shown
favourable results with NOM, this approach has not been adopted into clinical practice due to
concerns from physicians about the safety of NOM based on the limited evidence available.
Objectives: Therefore, the objective of this study is to conduct a pan-Canadian Phase II
trial to assess the safety of NOM for LRC.
Methods: All patients with LRC requiring surgery and a permanent colostomy being treated at
the participating centres will be assessed for complete clinical response (cCR) eight to ten
weeks following the completion of CRT by the treating surgeon. For the study, a cCR will be
defined as (i) no palpable tumour on digital rectal exam, (ii) no residual tumour defined as
white-yellow, flat scar on endoscopy, (iii) no residual tumour on MRI, (iv) no suspicious
mesorectal or extramesorectal lymph nodes on MRI and (v) normal CEA level. Patients who meet
all of these criteria for cCR will be invited to participate in the study. Patients who
consent to participate in the study will undergo active surveillance that will include DRE,
endoscopy and pelvic MRI every 3, 6, 9, 12, 18 and 24 months; CEA levels every 3, 6, 9, 12,
15, 18, 21, 24 months and CT chest/abdomen and pelvis every 6, 12, 18 and 24 months. The
primary outcome for the study will be the rate of local re-growth 2 years following the
completion of CRT. Local re-growth will be defined as failure to meet the cCR criteria at any
time point. NOM will be considered safe, if the rate of local re-growth is less than 30% two
years after the completion of CRT. The secondary outcomes for the study will be the rate of
distant recurrence, disease free and overall survival at 2 years.
Significance: The results of this study will be highly clinically relevant since it is
expected that NOM for LRC will be safe and will have significant potential to change clinical
practice in Canada and North America since approximately 30% of patients with LRC would be
able to safely avoid surgery and a permanent colostomy and have improved bowel and sexual
function and body image. Furthermore, widespread adoption of NOM has the potential to
increase health care capacity and decrease treatment costs by reducing the number of
surgeries, hospital admissions and costs associated with both surgery and long term surgical
morbidity.
View this trial on ClinicalTrials.gov
