The anti-retroviral agent, nelfinavir, demonstrates radiosensitising effects in pre-clinical models of pancreatic cancer. The primary objective of Stage 1 was to establish the maximum tolerated dose (MTD) of nelfinavir combined with capecitabine-chemoradiation (CRT) after gemcitabine+nab-paclitaxel (GEMABX) induction chemotherapy.
Patients with inoperable, histologically/cytologically proven LAPC and WHO performance status 0-1 were eligible for this rolling-six dose-escalation stage. After 3 cycles of induction GEMABX (28-day cycle of nab-paclitaxel 125mg/m2 and gemcitabine 1000mg/m2 on days 1, 8, and 15), patients with non-progressive disease had 1 further cycle followed by CRT (50.4Gy/28 fractions, capecitabine 830mg/m2 bd on radiotherapy days) and 1000mg or 1250mg nelfinavir bd continuously during CRT. Other outcomes included overall survival and progression-free survival.
27 patients were recruited from 8 UK centres (March 2016-June 2017). Median age was 62 years, 30% were male, 78% had head tumours, and 30% had biliary stents. Baseline median tumour diameter was 36mm. 67% commenced CRT. 11 patients received 1000mg and there was one dose-limiting toxicity (DLT) in this group: grade 3 acute coronary syndrome. The nelfinavir dose was escalated as per the rolling-six design. 7 patients received 1250mg nelfinavir and no DLTs were observed. During GEMABX, common grade ≥3 toxicities among participants were neutropenia (30%), fatigue (22%), and diarrhoea (15%). During CRT, grade ≥3 toxicities included fatigue (6%) and anorexia (6%). No grade 5 adverse events were reported in Stage 1. Survival analysis will be presented.
1250mg nelfinavir was recommended for combining with capecitabine-CRT in the ongoing randomised component of the trial (Stage 2).
Clinical trial identification
Legal entity responsible for the study
University of Oxford, UK.
Cancer Research UK, Celgene.
S. Mukherjee, P.G. Corrie: Research funding: Celgene. J. Bridgewater: Consultancy: Celgene. N. Patel: Part-time employee of GSK. All other authors have declared no conflicts of interest.