NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer

Inclusion Criteria:

- Histologically confirmed invasive well-moderately differentiated rectal adenocarcinoma
diagnosed within 90 days prior to enrollment.

- Tumour stage cT1-T3abN0 based on pelvic MRI

- cT1N0- tumour invasion into submucosa, no radiographic evidence of mesorectal
nodal metastasis, tumour deposits or vascular invasion.

- cT2N0 - tumour invasion into muscularis propria, no radiographic evidence of
mesorectal nodal metastasis, tumour deposits or vascular invasion.

- cT3a,bN0- tumour invasion through the muscularis propria no more than 5 mm into
the subserosa/perirectal tissue and clear of the circumferential radial margin
(CRM). Absence of radiographic evidence of mesorectal nodal metastasis, tumour
deposits or lymphovascular invasion.

- cN0 stage based on pelvic MRI. Any nodes ≥ 10 mm in longest dimension are considered
malignant, regardless of nodal morphology. For pelvic nodes < 10 mm in longest
dimension, if nodes are seen and are deemed to be morphologically benign in the
opinion of the radiologist and surgeon, the patient is eligible. Patients with visible
pelvic sidewall nodes are excluded

- M0 stage based on no evidence of metastatic disease by CT imaging.

- Mid to low-lying tumour eligible for local tumour excision in the opinion of the
treating surgeon.

- Age of at least 18 years.

- Medically fit to undergo radical surgery as per treating surgeon's discretion

- No contraindications to protocol chemotherapy.

- Adequate normal organ and marrow function as defined below (must be done within 30
days prior to enrolment):

- ANC ≥ 1.5 x 109/L

- platelet count ≥100 x 109/L

- bilirubin < 1.5 ULN, excluding Gilbert's syndrome

- Calculated creatinine clearance of ≥ 50 ml/min.

- Clearance to be calculated using Cockcroft formula: Males: 1.23 x (140 - age) x
weight (kg) - serum creatinine (μmol/l) ; Females: 1.05 x (140 - age) x weight
(kg) - serum creatinine (μmol/l)

- The patient must have an ECOG performance status of 0, 1.

- Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life
questionnaires.

- Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements. Each patient must sign a consent form prior to enrollment in
the trial to document their willingness to participate.

- Must be accessible for treatment and follow up. Patients registered on this trial must
be treated with chemotherapy and followed at the enrolling centre.

- Protocol treatment is to begin within 5 working days of patient enrolment.

- Women/men of childbearing potential must have agreed to use a highly effective
contraceptive method during and for 6 months after completion of chemotherapy.

Exclusion Criteria:

- Patient has pathologic high risk factors on either the initial biopsy specimen report
or follow up biopsy (if done): high histologic grade, mucinous histology, lymphatic or
vascular invasion.

- History of other malignancies, except: adequately treated non-melanoma skin cancer,
curatively treated in-situ cancer of the cervix, or other solid tumours curatively
treated with no evidence of disease for ≥ 5 years.

- Synchronous cancer.

- Prior treatment for rectal cancer.

- Previous pelvic radiation for any reason.

- Patients with known dihydropyrimidine dehydrogenase deficiency

- Treatment with other investigational drugs or anti-cancer therapy within 28 days prior
to enrolment.

- Clinically significant (i.e. active) cardiovascular disease for example cerebro
vascular accidents (< 6 months prior to enrolment), myocardial infarction (< 6 months
prior to enrolment), unstable angina, New York Heart Association (NYHA) grade II or
higher, congestive heart failure, serious cardiac arrhythmia requiring medication.

- Any contra-indications to undergo MRI imaging.