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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 - PubMed

Clinical Trial

. 2014 Dec;32(6):1197-203.

doi: 10.1007/s10637-014-0124-3. Epub 2014 Jun 12.

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Clinical Trial

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

Daniel W Bowles et al. Invest New Drugs. 2014 Dec.

Abstract

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/m(2) loading dose followed by 250 mg/m(2) 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.

Trial registration: ClinicalTrials.gov NCT01152628.

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References

    1. N Engl J Med. 2009 Sep 3;361(10):947-57 - PubMed
    1. Org Biomol Chem. 2004 Jul 7;2(13):1911-20 - PubMed
    1. Semin Oncol. 2004 Feb;31(1 Suppl 3):9-20 - PubMed
    1. Clin Cancer Res. 2012 Aug 1;18(15):4173-82 - PubMed
    1. J Clin Oncol. 2010 Feb 20;28(6):1075-83 - PubMed

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