Colorectal cancer (CRC) is one of the most common malignancies, and a leading cause of cancer death worldwide. Surgery is the only curative therapy available for locally advanced colon cancer (LACC), however, the disease is associated with a significant recurrence rate and even with adjuvant therapy its prognosis is far from satisfactory. Preoperative treatment strategy is an attractive concept in LACC because it has the theoretical advantages to eradicate micrometastases, to reduce tumor cell shedding during surgery, to allow the assessment of initial tumor response and could be better tolerated than adjuvant treatment. The results of the recently reported FOxTROT trial has shown that preoperative chemotherapy in LACC is feasible with no increase in surgical morbidity or mortality. The immune contexture of solid tumors has become an emerging hallmark of cancers. Recent evidences indicate that immune infiltrate (immunoscore) is an informative prognostic indicator in LACC. Moreover, it was demonstrated that immunoscore is also a stronger predictor of patient survival than microsatellite instability. Based on these considerations, we designed a window of opportunity study to determine the feasibility of nivolumab in the preoperative setting in pts with LACC.
Pts will receive nivolumab at a flat dosage of 240 mgs every two weeks on Day -28 and Day-14 (+/- one day) prior to planned surgery on Day 0 or up to + 7 days. An initial 6-pts safety run-in cohort will be followed by an expansion cohort, with a planned accrual of 16 pts. Postoperatively, standard adjuvant chemotherapy will be administered as recommended by guidelines. Primary objective is to determine the safety and feasibility of Nivolumab in the preoperative setting. The exploratory primary objective is the rate of pathological complete tumor regression, as well as correlative studies to determine molecular and immunophenotypic changes in tumor and peripheral blood samples as potential biomarkers of toxicity/efficacy. Secondary objective are tumor response rate defined by RECIST, postoperative complications, relapse-free survival, overall survival and metabolic response changes evaluated by FDG-PET-CT scan prior to surgery.
Clinical trial identification
Legal entity responsible for the study
Società Campana di Immunoterapia Oncologica (SCITO).
Società Campana di Immunoterapia Oncologica (SCITO) with funding from BMS.
All authors have declared no conflicts of interest.