CO.28: Neoadjuvant Chemotherapy, Excision and Observation (NEO) for early rectal cancer.

TPS724 Background: CO.28 is a phase II study which aims to determine if patients with stage I/II rectal cancer can be treated with induction chemotherapy (FOLFOX/CAPOX) and organ-preserving transanal microsurgery. Prior studies have explored the use of pelvic chemoradiation followed by transanal microsurgery as a means to increase organ preservation. However, pre-operative radiation may have acute and prolonged impacts such as wound complications and adverse on sphincter, sexual and urinary function. Moreover, patients who develop recurrence following this strategy are difficult to salvage as re-irradiation is not usually an option. There is virtually no prospective experience of neoadjuvant FOLFOX/CAPOX chemotherapy and excision for early rectal tumors. Methods: The primary objective is to determine the rate of organ preservation and the trial will be successful if more than 65% of patients avoid a formal rectal resection. In this two-staged phase II trial, patients are eligible if they have clinical N0 and T1-T3a/bN0M0 rectal tumors and no pathologic high risk features. After 6 cycles of q2weekly FOLFOX or 4 cycles of CAPOX, rectal endoscopy and pelvic MRI are repeated and if there is evidence of tumor response, patients proceed to tumor excision by Transanal Endoscopic Microsurgery (TEMS) or Transanal Minimally Invasive Surgery (TAMIS). It is required that participating surgeons have a minimum experience of 20 TEMS/TAMIS procedures and they are asked to submit an unedited video for central review. Pathologic ypT0 or ypT1N0 tumors are assigned to observation while ypT2+ or any ypN+ tumors are treated with radical surgery and total mesorectal excision (TME). Pre-operative pelvic radiation is suggested only for ypT3+ or node positive tumors. Endoscopic and cross-sectional imaging is repeated every 4-6 months for 36 months. Circulating tumor DNA (ctDNA) will be correlated with tumor response and relapse. A total of 58 patients will be accrued. Study Progress: The study was activated in Canada in late 2017 and at select US Cancer Centers in 2018, with total accrual to date of 4 patients. (NCT03259035) Clinical trial information: NCT03259035.