MK-0646 and Gemcitabine +/- Erlotinib for Patients With Advanced Pancreatic Cancer

Summary

Objectives: Primary Objectives: * Phase I: Determine the maximal tolerated dose (MTD) of MK-0646 in combination with gemcitabine or gemcitabine plus erlotinib and recommended phase II dose. * Phase II: * Assess progression-free survival (PFS) with a) gemcitabine plus MK-0646 b) gemcitabine plus erlotinib plus MK-0646 and c) gemcitabine plus erlotinib. * Explore IGF1 tissue level as a predictive biomarker for MK-0646 therapy in phase II expansion cohort. Secondary Objectives: * Assess overall response rate (ORR), treatment toxicity, and overall survival (OS) with the addition of MK-0646 to gemcitabine or gemcitabine plus erlotinib. * Correlate PFS and OS with IGF-1, IGFBP-3 levels and the expression of p-IRS, IGF-1R, EMT biomarkers, Akt, Erk, mTOR, and PI13k in tumor cells. * To assess the incidence of single nucleotide polymorphisms of the IgF1R pathway related genes (IGF1, IGF1R, IRS1 and IRS2). These genotypes will be correlated with the clinical endpoints of this study, including OS, ORR and PFS.

Timeline

Start

2008-11-13

Primary completion

2020-09-01

Completion

2020-09-01

Publications

• Abdel-Wahab R, Varadhachary GR, Bhosale PR, Wang X, Fogelman DR, Shroff RT, Overman MJ, Wolff RA, Javle M. Randomized, phase I/II study of gemcitabine plus IGF-1R antagonist (MK-0646) versus gemcitabine plus erlotinib with and without MK-0646 for advanced pancreatic adenocarcinoma. J Hematol Oncol. 2018 May 30;11(1):71. doi: 10.1186/s13045-018-0616-2.

Drugs

Indications