1091 - A phase I and randomized phase II trial to evaluate the efficacy and safety of nab-paclitaxel (nab-P) in combination with gemcitabine (G) for the treatment of patients with ECOG 2 advanced pancreatic cancer (PDAC).

Background

Nab-P+G significantly improved overall survival versus G in Patients (P) with Karnofsky index ≥70% metastatic PDAC (Von Hoff et al, 2013). The aim of this study was to select a tolerable dose -schedule of nab-P+G (Ph I), and to evaluate the efficacy of the selected regimen (Ph II) in patients with previously untreated ECOG-2 advanced PDAC.

Methods

In the phase1 portion of the study patients were randomized to one of 4 treatment regimens including G 1000 mg/m² and nab-P 150 mg/m² (arm B) or 125 mg/m² (arm D) days 1 and 15 every 28 days or same dose of G and nab-P 100 mg/m² (arm C) or 125 mg/m² (arm E) days 1, 8, and 15 every 28 days. The two safest regimens determined by analyzing hematological and non-hematological grade 3-4 toxicity, 30 and 60 days mortality, treatment discontinuation due to toxicity and dose intensity were selected for evaluation in the phase 2 portion of the study with 6 months overall survival (OS) as the primary endpoint.

Results

Regimens arm C and arm E (days 1, 8, 15 every 28 days schedule) were selected for the phase 2 portion of the study. A total of 221 patients (111 in arm C/110 in arm E) were enrolled. Median age was 71/68 y, 51/55% were male and 91/83% had metastatic disease (liver 63/62%). Most frequent grade 3-4 toxicity per arm were anemia (12/7%), neutropenia (32/30%), thrombocytopenia (7/11%), febrile neutropenia (3/4%), asthenia (14/16%) and neurotoxicity (11/16%). There were no significant differences in 6 months OS 63/69%, response rate (RR) 24/28% and median progression free survival (PFS) 5.7/6.7 months respectively in each arm.

Conclusions

Nab-P in combination with G, both at 100 and 125 mg/m² dose administered on a standard schedule of days 1, 8 and 15 is well tolerated and results in acceptable OS, RR and PFS in this fragile patient population.

Clinical trial identification

NCT02382263 EudraCT: 2012-003605-97

Legal entity responsible for the study

PH Research

Funding

Celgene

Disclosure

M. Hidalgo: Honoraria: Celgene. Consulting or advisory role: Celgene. Research funding: Celgene. Travel, accomodations: Celgene. R. Pazo-Cid: Consulting or advisory role: Celgene, Baxalta. A. Muñoz: Consulting or advisory role: Celgene. J. Sastre: Consulting or advisory role: Amgen, Sanofi, Bayer, Boheringer. Travel accomodations: Merck. Researcha funding: Amgen, Merck. All other authors have declared no conflicts of interest.