P-184 - nab-Paclitaxel (nab-P) plus gemcitabine (Gem) for patients with advanced pancreatic cancer who have cholestatic hyperbilirubinemia (CH) secondary to...

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Cancer in Special Situations
Pancreatic Cancer
Presenter H. Riess
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors H. Riess1, P.A. Philip2, V. Kunzmann3, T. Seufferlein4, D. McGovern5, P. Chen6, A. Romano7, R. Ramanathan8
  • 1Charité-Universitätsmedizin Berlin, Berlin/DE
  • 2Karmanos Cancer Center, Detroit/US
  • 3Universitätsklinikum Würzburg, Würzburg/DE
  • 4University of Ulm, Ulm/DE
  • 5Celgene, Stockley Park/UK
  • 6Celgene Corporation, Berkeley Heights/US
  • 7Celgene Corporation, Boudry/CH
  • 8Mayo Clinic, Scottsdale/US

Abstract

Introduction

Obstruction of the distal common bile duct is common in patients with advanced pancreatic cancer (PC) and can lead to elevated bilirubin levels. Treatment options are limited in this patient population. nab-P + Gem demonstrated superior efficacy vs Gem alone in a phase III trial of patients with metastatic PC, including the primary endpoint of overall survival (OS; median, 8.7 vs 6.6 months; HR 0.72; P < 0.001). nab-P + Gem has not been evaluated in patients with advanced PC and elevated bilirubin. This phase I study will evaluate the safety and pharmacokinetic (PK) profiles of nab-P + Gem in patients with advanced PC and CH secondary to bile duct obstruction.

Methods

Approximately 18 to 60 patients with advanced PC will be enrolled. Key eligibility criteria are summarized in Table 1. Patients will enter into 1 of 3 cohorts based on bilirubin level: cohort 1, > 1.5 to 2 × upper limit of normal (ULN); cohort 2, > 2 to 3 × ULN; and cohort 3, > 3 to 5 × ULN. Cohorts 2 and 3 will proceed only after a safety monitoring committee (SMC) has reviewed safety and PK data for the previous cohort and decided to proceed with the next respective cohort. This study follows a 3 + 3 dose-escalation scheme. The starting doses are 100 mg/m2 nab-P and 800 mg/m2 Gem for cohorts 1 and 2 and 75 mg/m2 and 600 mg/m2, respectively, for cohort 3. Treatment will be administered on days 1, 8, and 15 of each 28-day cycle. Patients will be treated until disease progression or unacceptable toxicity. The dose in each cohort will be modified according to tolerability as determined by the SMC. The primary endpoints are maximum tolerated dose for each cohort and PK profile. Secondary endpoints include investigator-assessed objective response rate, progression-free survival, OS, and safety. Secondary-endpoint efficacy analyses will be based on the treated population. Changes in serum CA19-9 level from baseline will be evaluated as an exploratory endpoint. Safety analyses will include patients treated with ≥ 1 dose and having ≥ 1 safety assessment. Enrollment is ongoing. ClinicalTrials.gov: NCT02267707.

Table: P-184. Key Eligibility Criteria