1. 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.
- Author
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Bowles, Daniel, Senzer, Neil, Hausman, Diana, Peterson, Scott, Vo, Alex, Walker, Luke, Cohen, Roger, and Jimeno, Antonio
- Subjects
ANTINEOPLASTIC agents ,TUMOR markers ,ACADEMIC medical centers ,COMBINATION drug therapy ,COLON tumors ,EPIDERMAL growth factor ,HEAD tumors ,METASTASIS ,GENETIC mutation ,NECK tumors ,HEALTH outcome assessment ,RECTUM tumors ,RESEARCH funding ,SAFETY ,TREATMENT effectiveness ,DESCRIPTIVE statistics ,THERAPEUTICS ,INVESTIGATIONAL drugs - 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 loading dose followed by 250 mg/m 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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