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A phase I/II study of the Src inhibitor saracatinib (AZD0530) in combination with gemcitabine in advanced pancreatic cancer

  • PHASE II STUDIES
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Summary

Aim This phase I/II study of saracatinib in combination with gemcitabine in patients with advanced pancreatic cancer was conducted by the NCIC Clinical Trials Group. The aims were to define the recommended phase II dose (RP2D) of saracatinib when combined with gemcitabine, and assess the efficacy of this combination in advanced pancreatic cancer. Patients and Methods Eligibility criteria included locally advanced or metastatic pancreatic adenocarcinoma and no prior chemotherapy. In phase I saracatinib was escalated in combination with gemcitabine (1000 mg/m2) to determine the recommended phase II dose (RP2D). The study was then expanded to a single arm phase II trial using a Simon 2-stage design. The primary endpoint was objective tumor response (OR) plus stable disease ≥4 months (SD4) rate; if ≥8 patients had OR+SD4, the study would proceed to stage 2. Results Thirteen patients were enrolled into the phase I portion of this study. Saracatinib 175 mg PO daily was chosen as the RP2D in combination with gemcitabine. Twenty-one additional patients were then enrolled at the RP2D (phase II). Of the 22 response evaluable patients treated at the RP2D, 9 patients (40.9%) had progressive disease, 6 patients (27.3%) had stable disease for less than 4 months, 5 patients (22.7%) had SD4, and 2 patients (9.1%) had a partial response to treatment. Objective criteria for continuing to stage 2 were thus not met and the trial was closed following the accrual of 34 patients. Conclusion Saracatinib 175 mg daily in combination with gemcitabine is well tolerated but the combination did not improve efficacy over what would be expected from gemcitabine alone.

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Funding

This study was supported by funding from the Canadian Cancer Society. AstraZeneca provided saracatinib and partial funding to support the study.

Conflicts of Interest

Lesley Seymour received research funding from Astra Zeneca for this trial and has shares with Astra Zeneca. Derek Jonker attended an advisory board for Astra Zeneca.

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Authors and Affiliations

  1. Division of Medical Oncology and Hematology, Rm 5-708, Princess Margaret Hospital, 610 University Avenue, Toronto, M5G2M9, Canada

    Daniel J. Renouf, Malcolm J. Moore, David Hedley, Eric Chen & Bernadette Southwood

  2. British Columbia Cancer Agency - Vancouver Cancer Centre, Vancouver, Canada

    Sharlene Gill

  3. Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada

    Derek Jonker & Rakesh Goel

  4. Algoma District Cancer Program, Sault Ste. Marie, Canada

    David Walde

  5. NCIC Clinical Trials Group, Kingston, Canada

    Isabelle Gauthier, Wendy Walsh, Lynn McIntosh & Lesley Seymour

Authors
  1. Daniel J. Renouf
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  2. Malcolm J. Moore
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  3. David Hedley
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  4. Sharlene Gill
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  5. Derek Jonker
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  6. Eric Chen
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  7. David Walde
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  8. Rakesh Goel
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  9. Bernadette Southwood
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  10. Isabelle Gauthier
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  11. Wendy Walsh
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  12. Lynn McIntosh
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  13. Lesley Seymour
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Corresponding author

Correspondence to Malcolm J. Moore.

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Renouf, D.J., Moore, M.J., Hedley, D. et al. A phase I/II study of the Src inhibitor saracatinib (AZD0530) in combination with gemcitabine in advanced pancreatic cancer. Invest New Drugs 30, 779–786 (2012). https://doi.org/10.1007/s10637-010-9611-3

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  • DOI: https://doi.org/10.1007/s10637-010-9611-3

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