A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma

Ann Oncol. 2013 Jun;24(6):1567-73. doi: 10.1093/annonc/mdt002. Epub 2013 Feb 13.

Abstract

Background: PEP02 is a novel highly stable liposomal nanocarrier formulation of irinotecan. This randomized phase II study evaluated the efficacy and safety of single agent PEP02 compared with irinotecan or docetaxel in the second-line treatment of advanced oesophago-gastric (OG) cancer.

Patients and methods: Patients with locally advanced/metastatic disease who had failed one prior chemotherapy regimen were randomly assigned to PEP02 120 mg/m(2), irinotecan 300 mg/m(2) or docetaxel (Taxotere) 75 mg/m(2) every 3 weeks. The primary end point was objective response rate (ORR). Simon's two-stage design was used and the ORR of interest was 20% (α = 0.05, type II error β = 0.10, null hypothesis of ORR was 5%).

Results: Forty-four patients per arm received treatment, and 124 were assessable for response. The ORR statistical threshold for the first stage was reached in all arms. In the intent-to-treat (ITT) population, ORRs were 13.6% (6/44), 6.8% (3/44) and 15.9% (7/44) in the PEP02, irinotecan and docetaxel arms, respectively. The median progression-free survival (PFS) and overall survival were similar between the trial arms. Commonest grade 3-4 adverse event reported was diarrhoea in the PEP02 and irinotecan groups (27.3% versus 18.2%).

Conclusion: The ORR associated with PEP02 was comparable with docetaxel and numerically greater than that of irinotecan. PEP02 warrants further evaluation in the advanced gastric cancer setting.

Trial registration: ClinicalTrials.gov NCT00813072.

Keywords: docetaxel; irinotecan; liposomal irinotecan; oesophago-gastric cancer; phase II; second line.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / mortality
  • Adult
  • Aged
  • Aged, 80 and over
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Docetaxel
  • Drug Carriers / administration & dosage*
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / mortality
  • Esophagogastric Junction / drug effects
  • Esophagogastric Junction / pathology*
  • Female
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Nanocapsules / administration & dosage
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / mortality
  • Survival Rate / trends
  • Taxoids / administration & dosage*

Substances

  • Drug Carriers
  • Nanocapsules
  • Taxoids
  • Docetaxel
  • Irinotecan
  • Camptothecin

Associated data

  • ClinicalTrials.gov/NCT00813072