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Investigational New Drugs

, Volume 30, Issue 4, pp 1614–1620 | Cite as

A phase 2 study of oral MKC-1, an inhibitor of importin-β, tubulin, and the mTOR pathway in patients with unresectable or metastatic pancreatic cancer

  • Jason E. Faris
  • Jamie Arnott
  • Hui Zheng
  • David P. Ryan
  • Thomas A. Abrams
  • Lawrence S. Blaszkowsky
  • Jeffrey W. Clark
  • Peter C. Enzinger
  • Aram F. Hezel
  • Kimmie Ng
  • Brian M. Wolpin
  • Eunice L. Kwak
PHASE II STUDIES

Summary

Background MKC-1 is an orally available cell cycle inhibitor with downstream targets that include tubulin and the importin-β family. We conducted an open-label Phase II study with MKC-1 in patients with advanced pancreatic cancer. Methods Eligibility criteria included unresectable or metastatic pancreatic cancer, performance status of 1 or better, and failure of at least one prior regimen of chemotherapy. MKC-1 was administered orally, twice daily, initially at 100 mg/m2 dosing for 14 consecutive days of a 28-day cycle. This schedule was modified during the trial to fixed and continuous dosing of 150 mg per day. Results 20 of an original target of 33 patients were accrued, with a median age of 61 (range 44–81). No objective responses were observed, with one patient demonstrating stable disease. Overall survival was 101 days from the start of MKC-1 administration, and median time to progression was 42 days. The most common adverse events listed as related or possibly related to MKC-1 administration were hematologic toxicities and fatigue. One patient developed grade 5 (fatal) pancytopenia. Grade 3 and 4 events included cytopenias (lymphopenia, anemia), hyperbilirubinemia, pneumonia, mucositis, fatigue, infusion reaction, anorexia, and hypoalbuminemia. Conclusions MKC-1 administration was associated with substantial toxicity and did not demonstrate sufficient activity in patients with advanced pancreatic cancer to justify further exploration in this patient population.

Keywords

Pancreatic cancer Phase II MKC-1 Importin Tubulin 

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Jason E. Faris
    • 1
  • Jamie Arnott
    • 4
  • Hui Zheng
    • 3
  • David P. Ryan
    • 2
  • Thomas A. Abrams
    • 5
  • Lawrence S. Blaszkowsky
    • 2
  • Jeffrey W. Clark
    • 2
  • Peter C. Enzinger
    • 5
  • Aram F. Hezel
    • 6
  • Kimmie Ng
    • 5
  • Brian M. Wolpin
    • 5
  • Eunice L. Kwak
    • 2
  1. 1.Department of Medical OncologyMassachusetts General Hospital Cancer CenterBostonUSA
  2. 2.Department of Medical OncologyMassachusetts General Hospital Cancer CenterBostonUSA
  3. 3.Biostatistics CenterMassachusetts General HospitalBostonUSA
  4. 4.Entremed, Inc.DurhamUSA
  5. 5.Department of Medical OncologyDana Farber Cancer InstituteBostonUSA
  6. 6.James P. Wilmot Cancer CenterUniversity of Rochester School of MedicineRochesterUSA

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