Trials in Progress Poster Session
FOxTROT: Randomized phase II study of neoadjuvant chemotherapy with or without an anti-EGFR monoclonal antibody for locally advanced, operable colon cancer.
Background: For many patients with high-risk, operable colon cancer, surgical excision followed by adjuvant CT fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Micrometastases may be more readily eradicated by neoadjuvant CT than CT given after the delay and immunological stress of surgery. Shrinking the tumor before surgery may also reduce the risk of incomplete surgical excision, and tumor cell shedding during surgery. Preoperative CT and radiotherapy are surprisingly more effective than postoperative treatment in several other cancers, notably rectal, and neoadjuvant CT has become feasible in colon cancer now that response rates exceed 50% and radiological staging is more accurate. Preoperative CT also provides a unique opportunity to identify tumor markers predictive of response to CT and anti-EGFR therapy.
Methods: FOxTROT (Fluoropyrimidine, Oxaliplatin and Targeted Receptor Pre-Operative Therapy) has randomized 98 patients (target=150) with radiologically staged T4 or “T3 bad” (extramural depth of ≥ 5 mm), M0, resectable colon cancer 2:1 to receive the first 6 weeks of OxMdG (oxaliplatin 85 mg/m2, l-folinic acid 175 mg, 5-FU 400 mg/m2 bolus then 2,400 mg/m2 by 46h infusion) CT preoperatively or all 24 weeks postoperatively. KRAS wildtype patients are randomised 1:1 to receive an anti- EGFR monoclonal antibody, panitumumab (6 mg/kg; 2-weekly) with the first 6 weeks of CT, or control. Outcomes are feasibility of preoperative KRAS testing, radiological staging, randomization and CT, toxicity and perioperative morbidity with neoadjuvant CT, accuracy of radiological compared to pathological stage, accuracy of radiological eligibility criteria in selecting high-risk patients suitable for CT and excluding low-risk cancers. If neoadjuvant CT of colon cancer is feasible, FOxTROT will proceed to a phase III trial, with target 900 patients and integrated studies of potential molecular markers of response. Primary outcomes will be 2-year recurrence for pre-operative CT, pathological downstaging for panitumumab, and value of molecular markers in predicting response.
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