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A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck

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Summary

Background This phase I, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), and antitumor activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with cetuximab in patients with incurable colorectal cancer or squamous cell carcinoma of the head and neck. Methods PX-866 was administered at escalating doses (6–8 mg daily) combined with cetuximab given at a 400 mg/m2 loading dose followed by 250 mg/m2 weekly. A “3 + 3” study design was used. Prior therapy with anti-EGFR therapies, including cetuximab, was allowed. Results Eleven patients were enrolled. The most frequent treatment-emergent adverse event was diarrhea (90.1 %), followed by hypomagnesemia (72.2 %), vomiting (72.2 %), fatigue (54.5 %), nausea (54.5 %), rash (45.5 %) and peripheral edema (40 %). No dose limiting toxicities were observed. The RP2D was 8 mg, the same as the single-agent PX-866 MTD. Best responses in 9 evaluable patients were: 4 partial responses (44.4 %), 4 stable disease (44.4 %), and 1 disease progression (11.1 %). The median progression free survival was 106 days (range: 1–271). Conclusion Treatment with PX-866 and cetuximab was tolerated with signs of anti-tumor activity. Further development of this combination is warranted.

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Acknowledgments

The authors wish to thank the patients, caregivers, and clinical and research personnel who made this work possible. The authors wish to thank Dawn Pearson who provided medical writing services on behalf of Oncothyreon Inc.

This work was supported by Oncothyreon Inc and the University of Colorado Cancer Center (P30CA046934).

Alex Vo, Scott Peterson, Luke Walker, and Diana Hausman are employees of Oncothyreon Inc.; Antonio Jimeno has received laboratory research support from Oncothyreon Inc.; Dr. Cohen has been a consultant for Oncothyreon Inc

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Authors and Affiliations

  1. Division of Medical Oncology, University of Colorado School of Medicine, 12801 East 17th Avenue MS 8117 Aurora, Denver, CO, 80045, USA

    Daniel W. Bowles & Antonio Jimeno

  2. Mary Crowley Cancer Research Center, Dallas, TX, USA

    Neil Senzer

  3. Oncothyreon Inc, 2601 Fourth Avenue, Seattle, WA, USA

    Diana Hausman, Scott Peterson, Alex Vo & Luke Walker

  4. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Roger B. Cohen

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  1. Daniel W. Bowles
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Correspondence to Daniel W. Bowles.

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Bowles, D.W., Senzer, N., Hausman, D. et al. A multicenter phase 1 study of PX-866 and cetuximab in patients with metastatic colorectal carcinoma or recurrent/metastatic squamous cell carcinoma of the head and neck. Invest New Drugs 32, 1197–1203 (2014). https://doi.org/10.1007/s10637-014-0124-3

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  • DOI: https://doi.org/10.1007/s10637-014-0124-3

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