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Investigational New Drugs

, Volume 30, Issue 3, pp 1158–1163 | Cite as

A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) adenocarcinoma: a trial of the PMH phase II consortium

  • Helen J. MackayEmail author
  • Heather J. Au
  • Elaine McWhirter
  • Thierry Alcindor
  • Andrea Jarvi
  • Katrina MacAlpine
  • Lisa Wang
  • John J. Wright
  • Amit M. Oza
PHASE II STUDIES

Summary

Purpose The Src family of kinases may play a role in the development and progression of gastric cancer. We evaluated the activity and safety of saracatinib an oral, anilinoquinazolone, non-receptor tyrosine kinase inhibitor targeting Src kinases, in patients with metastatic or locally advanced gastric carcinoma. Methods Eligible patients who had received ≤1 prior line of chemotherapy for metastatic disease received saracatinib 175 mg/day of a 28 day cycle until progression. The primary endpoint was the objective response and/or prolonged stable disease rate (pSD ≥ 16 weeks). Results Ten patients with gastric carcinoma and 11 with adenocarcinoma of the gastroesophageal junction received a median of 2 cycles (range 1–10 cycles) of treatment per patient. 17 patients were evaluable for response. No objective response was seen. One patient experienced prolonged Stable disease (pSD). Three patients had SD and 13 progressive disease. Median overall survival was 7.8 months (95% CI, 3.9–12.2 months) and median time to progression was 1.8 months (95% CI: 1.5–1.9 months). Grade 3 events possibly related to saracatinib included: fatigue (2 patients), hypoxia (2) anemia (3) and lymphopenia (2). Conclusion Saracatinib has insufficient activity as a single agent in patients with advanced gastric adenocarcinoma to warrant further investigation. Further development in gastric cancer would require rational drug combinations or identification of a tumor phenotype sensitive to Src inhibition.

Keywords

Gastric cancer Phase II Saracatinib (AZD0530) Src kinase inhibitor 

Notes

Acknowledgements

This trial was supported by funding from, and drug was supplied by the Cancer Therapeutics Evaluation Program, US National Cancer Institute

Conflict of interest statement

None of the authors of this manuscript have any conflict of interest to declare.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Helen J. Mackay
    • 1
    • 7
    Email author
  • Heather J. Au
    • 2
  • Elaine McWhirter
    • 3
  • Thierry Alcindor
    • 4
  • Andrea Jarvi
    • 5
  • Katrina MacAlpine
    • 5
  • Lisa Wang
    • 1
  • John J. Wright
    • 6
  • Amit M. Oza
    • 5
  1. 1.Department of Medical Oncology, Princess Margaret HospitalUniversity of TorontoOntarioCanada
  2. 2.Cross Cancer InstituteUniversity of AlbertaEdmontonCanada
  3. 3.Juravinski Cancer CentreHamiltonCanada
  4. 4.McGill University Health CentreMontrealCanada
  5. 5.Department of Medical Oncology, Princess Margaret Hospital, Drug Development ProgramUniversity of TorontoOntarioCanada
  6. 6.National Cancer InstituteRockvilleUSA
  7. 7.Princess Margaret HospitalTorontoCanada

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