A Phase Ii Study Of Complete Neoadjuvant Therapy In Rectal Cancer (Contre): The Brown University Oncology Group

335 Background: While preoperative chemoradiation followed by surgery is the standard approach for patients (pts) with newly diagnosed clinical stage II-III rectal cancer, many are unable to tolerate postoperative adjuvant chemotherapy which may compromise disease-free and overall survival. CONTRE is a multicenter phase II study designed to determine the feasibility of administering all chemotherapy prior to surgery and to assess its impact on pathologic complete response (pCR) and complete (R0) resection Methods: Pts with T3-4 and/or N1-2 rectal cancer, staged by endorectal ultrasound (ERUS) and pelvic MRI, receive modified (m) FOLFOX6 every 2 weeks x 8 cycles, followed by repeat MRI and proctoscopy to assess response. Pts then receive 50.4 Gy IMRT with 5-FU 225 mg/m2/day or capecitabine 825mg/m2 BID, 5 days per week during radiation, followed by surgery 4-8 weeks later. Results: Thus far, we have enrolled 36 of a planned 39 pts (median age 58, range 30-79; T2-1, T3-30, T4-2; N1-20, N2-7). 28 of the first 30 (93%) completed 8 cycles of mFOLFOX6. 26 pts have completed chemoradiation while 2 chose to proceed directly to surgery. All patients opted to receive capecitabine during radiation. Grade 3/4 toxicities during chemotherapy and chemoradiation have included diarrhea (16%) and neutropenia (12%), with grade 3 renal and cardiac toxicities reported in one patient each. A clinical complete response after chemotherapy alone was achieved in 3 of 29 (10%). Of the first 21 pts undergoing surgery, pCR has been achieved in 6 (29%) and R0 resections in 100%. Thus far, all pts have been able to undergo sphincter-sparing resections. Study accrual will be completed by the meeting. Conclusions: A larger proportion of stage II-III rectal cancer pts are able to complete mFOLFOX6 (>90% in our cohort) when administered prior to chemoradiation and surgery. Complete neoadjuvant treatment may represent a well-tolerated alternative to the current standard treatment sequence and a platform for the evaluation of novel therapeutics such as targeted agents during preoperative therapy. Funded in part by LIFEcycle, Inc. Clinical trial information: NCT01363843.