A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression

D. Li, S. Pant, D. P. Ryan, D. Laheru, N. Bahary, T. Dragovich, P. J. Hosein, L. Rolfe, M. W. Saif, J. Lavalle, K. H. Yu, M. A. Lowery, A. Allen, E. M. O'Reilly

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Abstract

Background Nucleotide transporters such as human equilibrative nucleoside transporter-1 (hENT1) play a major role in transporting gemcitabine into cells. CO-1.01 (gemcitabine-5′-elaidate) is a novel cytotoxic agent consisting of a fatty acid derivative of gemcitabine, which is transported intracellularly independent of hENT1. CO-1.01 was postulated to have efficacy as a second-line treatment in gemcitabine-refractory pancreatic adenocarcinoma in patients with negative tumor hENT1 expression.

Methods Eligibility criteria included patients with either a newly procured or archival biopsy tumor confirming the absence of hENT1 and either gemcitabine-refractory metastatic pancreas adenocarcinoma or with progression of disease following resection during or within 3 months of adjuvant gemcitabine therapy. Patients were treated with intravenous infusion of CO-1.01 dosed at 1250 mg/m2 on Days 1, 8, and 15 of a 4-week cycle. The primary end point was disease control rate (DCR).

Results Nineteen patients were enrolled of which 18 patients were evaluable for efficacy assessment. Thirteen patients (68%) had liver metastases, 6 (32%) had lymph node metastases, and 10 (53%) had lung metastases. Two of 18 patients (11%) achieved disease control. The median survival time was 4.3 (95% CI 2.1-8.1) months. All patients experienced at least one treatment-related adverse event with the majority of events being mild or moderate.

Conclusion This study did not meet its primary endpoint and no efficacy signal was identified for CO-1.01 in treating progressive metastatic pancreas adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)398-402
Number of pages5
JournalPancreatology
Volume14
Issue number5
DOIs
StatePublished - Sep 1 2014

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Keywords

  • Biomarker
  • CO-1.01
  • Disease-control rate
  • Gemcitabine-refractory
  • Pancreas adenocarcinoma
  • hENT1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

Cite this

Li, D., Pant, S., Ryan, D. P., Laheru, D., Bahary, N., Dragovich, T., Hosein, P. J., Rolfe, L., Saif, M. W., Lavalle, J., Yu, K. H., Lowery, M. A., Allen, A., & O'Reilly, E. M. (2014). A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression. Pancreatology, 14(5), 398-402. https://doi.org/10.1016/j.pan.2014.07.003