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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

  • PHASE II STUDIES
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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.

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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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Authors and Affiliations

  1. Department of Medical Oncology, Princess Margaret Hospital, University of Toronto, Ontario, Canada

    Helen J. Mackay & Lisa Wang

  2. Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada

    Heather J. Au

  3. Juravinski Cancer Centre, Hamilton, ON, Canada

    Elaine McWhirter

  4. McGill University Health Centre, Montreal, QC, Canada

    Thierry Alcindor

  5. Department of Medical Oncology, Princess Margaret Hospital, Drug Development Program, University of Toronto, Ontario, Canada

    Andrea Jarvi, Katrina MacAlpine & Amit M. Oza

  6. National Cancer Institute, Rockville, MD, USA

    John J. Wright

  7. Princess Margaret Hospital, 610 University Ave, Toronto, ON, Canada, M5G 2M9

    Helen J. Mackay

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  1. Helen J. Mackay
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  2. Heather J. Au
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  3. Elaine McWhirter
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  4. Thierry Alcindor
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  5. Andrea Jarvi
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  7. Lisa Wang
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  9. Amit M. Oza
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Correspondence to Helen J. Mackay.

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Mackay, H.J., Au, H.J., McWhirter, E. et al. 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. Invest New Drugs 30, 1158–1163 (2012). https://doi.org/10.1007/s10637-011-9650-4

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  • DOI: https://doi.org/10.1007/s10637-011-9650-4

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