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Investigational New Drugs

, Volume 33, Issue 4, pp 977–984 | Cite as

Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer

  • S. M. ReddyEmail author
  • S. Kopetz
  • J. Morris
  • N. Parikh
  • W. Qiao
  • M. J. Overman
  • D. Fogelman
  • I. Shureiqi
  • C. Jacobs
  • Z. Malik
  • C. A. Jimenez
  • R. A. Wolff
  • J. L. Abbruzzese
  • G. Gallick
  • C. Eng
PHASE II STUDIES

Summary

Background Src has a critical role in tumor cell migration and invasion. Increased Src activity has been shown to correlate with disease progression and poor prognosis, suggesting Src could serve as a therapeutic target for kinase inhibition. Saracatinib (AZD0530) is a novel selective oral Src kinase inhibitor. Methods Metastatic colorectal cancer patients who had received one prior treatment and had measurable disease were enrolled in this phase 2 study. Saracatinib was administered at 175 mg by mouth daily for 28 day cycles until dose-limiting toxicity or progression as determined by staging every 2 cycles. The primary endpoint was improvement in 4 month progression-free survival. Design of Thall, Simon, and Estey was used to monitor proportion of patients that were progression free at 4 months. The trial was opened with plan to enroll maximum of 35 patients, with futility assessment every 10 patients. Results A total of 10 patients were enrolled between January and November 2007. Further enrollment was stopped due to futility. Median progression-free survival was 7.9 weeks, with all 10 patients showing disease progression following radiographic imaging. Median overall survival was 13.5 months. All patients were deceased by time of analysis. Observed adverse events were notable for a higher than expected number of patients with grade 3 hypophosphatemia (n = 5). Conclusion Saracatinib is a novel oral Src kinase inhibitor that was well tolerated but failed to meet its primary endpoint of improvement in 4 month progression-free survival as a single agent in previously treated metastatic colorectal cancer patients.

Keywords

Saracatinib Src inhibitor Colorectal cancer Phase 2 AZD0530 Colon cancer Src kinase 

Notes

Compliance with Ethical Standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

This study was presented at AACR 2008 and funded by the National Cancer Institute (NCI Protocol #7565, NSC735464).

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • S. M. Reddy
    • 1
    Email author
  • S. Kopetz
    • 2
  • J. Morris
    • 3
  • N. Parikh
    • 4
  • W. Qiao
    • 3
  • M. J. Overman
    • 2
  • D. Fogelman
    • 2
  • I. Shureiqi
    • 2
  • C. Jacobs
    • 2
  • Z. Malik
    • 5
  • C. A. Jimenez
    • 6
  • R. A. Wolff
    • 2
  • J. L. Abbruzzese
    • 7
  • G. Gallick
    • 8
  • C. Eng
    • 2
  1. 1.Hematology-Oncology Fellow, Division of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Department of Gastrointestinal Medical OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Biostatistics & Applied MathThe University of Texas MD Anderson Cancer CenterHoustonUSA
  4. 4.Department of Genitourinary Medical Oncology-ResearchThe University of Texas MD Anderson Cancer CenterHoustonUSA
  5. 5.Norton Cancer InstituteLouisvilleUSA
  6. 6.Department of Pulmonary MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  7. 7.Duke Cancer InstituteDurhamUSA
  8. 8.Department of Cancer BiologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

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