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Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001)

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Abstract

Purpose

Vatalanib (PTK 787/ZK22584) is an oral poly-tyrosine kinase inhibitor with strong affinity for platelet-derived growth factor and vascular endothelial growth factor (VEGF) receptors. We conducted an open-label, phase II multicenter therapeutic trial investigating the efficacy and tolerability of vatalanib in patients with metastatic or advanced pancreatic cancer who failed first-line gemcitabine-based therapy.

Methods

Vatalanib treatment consisted of a twice daily oral dosing using a “ramp-up schedule,” beginning with 250 mg bid during week 1,500 mg bid during week 2, and 750 mg bid on week three and thereafter. The primary objective of this study was to evaluate the 6-month survival rate.

Results

Sixty-seven patients were enrolled. The median age was 64, and 66 % (N = 43) had only one prior regimen. Common grade 3/4 adverse events included hypertension (20 %; N = 13), fatigue (17 %; N = 11), abdominal pain (17 %; N = 11), and elevated alkaline phosphatase (15 %; N = 10). Among the 65 evaluable patients, the 6-month survival rate was 29 % (95 % CI 18–41 %) and the median progression-free survival was 2 months. Fifteen patients survived 6 months or more. Two patients had objective partial responses, and 28 % of patients had stable disease. Changes in biomarkers including soluble VEGF and vascular endothelial growth factor receptor did not correlate with response to drug.

Conclusion

Vatalanib was well tolerated as a second-line therapy and resulted in favorable 6-month survival rate in patients with metastatic pancreatic cancer, compared with historic controls.

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Acknowledgments

The authors are thankful to Ms. Amy Stoll from TGEN/PCRT, Drs. Denise Roe and Haiyan Cui from Biometry Core at the University of Arizona Cancer Center, and Ms. Tamara Burkhead for the help with trial coordination and manuscript preparation. This work was supported in part by P50 CA95060 (E. Gerner), CA017094, and P30 CA023074 from the National Cancer Institute to University of Arizona Cancer Center (TD and AFB), for correlative science. Additional support for imaging studies was provided by GE Healthcare. Supported by Investigator Initiated Grant (from Novartis) to T.D.

Conflict of interest

None.

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Authors and Affiliations

  1. Banner MD Anderson Cancer Center, 1900 N. Higley Road, Gilbert, AZ, 85234, USA

    T. Dragovich & F. Dayyani

  2. The University of Arizona Cancer Center, Tucson, AZ, USA

    T. Dragovich, A. F. Baker & N. Raghunand

  3. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA

    D. Laheru

  4. Cancer Research and Biostatistics, Seattle, WA, USA

    V. Bolejack & J. Crowley

  5. South Texas Oncology Hematology, San Antonio, TX, USA

    L. Smith

  6. Virginia Piper Cancer Institute, Minneapolis, MN, USA

    J. Seng

  7. Sarah Cannon Cancer Center, Nashville, TN, USA

    H. Burris

  8. Tower Cancer Research Foundation, Beverly Hills, CA, USA

    P. Rosen

  9. Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    M. Hidalgo

  10. Medical College of Wisconsin, Milwaukee, WI, USA

    P. Ritch

  11. Virginia G. Piper Cancer Center at Scottsdale Healthcare, Scottsdale, AZ, USA

    D. D. Von Hoff

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  1. T. Dragovich
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  2. D. Laheru
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  14. D. D. Von Hoff
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Correspondence to T. Dragovich.

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Dragovich, T., Laheru, D., Dayyani, F. et al. Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001). Cancer Chemother Pharmacol 74, 379–387 (2014). https://doi.org/10.1007/s00280-014-2499-4

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  • DOI: https://doi.org/10.1007/s00280-014-2499-4

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