High plasma levels of interleukin-6 (IL-6) are found in patients with pancreatic cancer (PC) and in part facilitate systemic inflammation cascade and cachexia. The current phase 2 trial (PACTO) will evaluate the efficacy and safety of nab-paclitaxel and gemcitabine with or without tocilizumab, an IL-6R inhibitor, as first-line treatment in patients with advanced PC.
Eligible patients with chemotherapy-naïve locally advanced or metastatic PC (n = 140), ECOG performance status (PS) of 0–1, and presence of a systemic inflammatory response (elevated C-reactive protein [CRP] levels or a modified Glasgow Prognostic Score [mGPS] of 1 or 2) will be randomized 1:1 (stratified by PS [PS 0 vs PS 1] and stage [locally advanced vs metastatic disease]) to receive tocilizumab 8 mg/kg on day 1 in combination with nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 or nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Before randomization begins, the first six patients enrolled will be treated in the investigational arm for safety assessment and will not be included in the final analysis. The primary endpoint is overall survival (OS) rate at 6 months. Assuming a 6 month OS rate of 67% in the reference arm and an improvement by at least 20% by the intervention (corresponding to a 6 month OS of 80%), a total of 140 patients are needed (1:1 allocation) to obtain a statistical power of 80% with a significance level of 5%. Secondary endpoints include change from baseline PS, assessed by both investigator and patient, progression-free survival, OS, tumor response per RECIST 1.1, safety and assessment of quality of life by EORTC QLQ-C30. Patients will be assessed by CT scan every 8 weeks. Exploratory endpoints include circulating tumor DNA KRAS, body composition changes, plasma biomarkers of cachexia and inflammation. Treatment will continue as long as it is tolerated until disease progression. Enrollment was initiated in January 2017 and is ongoing.
Clinical trial identification
Legal entity responsible for the study
Herlev & Gentofte Hospital
All authors have declared no conflicts of interest.