scholarly journals Phase I dose-escalation study to determine the safety, pharmacokinetics and pharmacodynamics of brivanib alaninate in combination with full-dose cetuximab in patients with advanced gastrointestinal malignancies who have failed prior therapy

2011 ◽  
Vol 105 (1) ◽  
pp. 44-52 ◽  
Author(s):  
C R Garrett ◽  
L L Siu ◽  
A El-Khoueiry ◽  
J Buter ◽  
C M Rocha-Lima ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dose Escalation Study ◽  
Gastrointestinal Malignancies ◽  
Full Dose ◽  
Prior Therapy ◽  
Brivanib Alaninate

A phase I study of BMS-582664 (brivanib alaninate), an oral dual inhibitor of VEGFR and FGFR tyrosine kinases, in combination with full-dose cetuximab in patients (pts) with advanced gastrointestinal malignancies (AGM) who failed prior therapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14018-14018 ◽  
Author(s):  
C. R. Garrett ◽  
L. L. Siu ◽  
G. Giaccone ◽  
A. El-Khoueiry ◽  
J. Marshall ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Fdg Pet ◽  
Kinase Inhibitor ◽  
Imaging Modality ◽  
Single Agent ◽  
Dual Inhibitor ◽  
Gastrointestinal Malignancies ◽  
Full Dose ◽  
Prior Therapy

14018 Background: Brivanib is an oral prodrug of BMS-540215, a dual tyrosine kinase inhibitor of VEGFR and FGFR signaling. Prior studies have validated both VEGF and EGF signaling pathways as targets in AGM. The MTD of single-agent brivanib is 800 mg qd (ASCO #3051, 2006). Methods: An open-label Phase I dose-escalation study of brivanib in combination with cetuximab was conducted in pts with AGM who failed prior therapy. Brivanib was given po Day 1 and qd from Day 8, starting at 320 mg. Cetuximab was given IV Day 8 (400 mg/m2) then weekly (250 mg/m2). Dose escalation of brivanib continued to 800 mg qd, when an expansion cohort for pts with colorectal cancer (CRC) was opened for additional safety and efficacy. Fresh tissue and blood sampling for biomarker and pharmacokinetic (PK) analysis was performed. FDG-PET was obtained at Baseline X 2, Days 15 and 56. Tumor response (modified WHO) was evaluated q 8 weeks. Results: 18 pts (15 CRC, 2 esophageal, 1 other) were treated with 320, 600 or 800 mg qd of brivanib in combination with cetuximab for a median of 8 weeks (range 1 - 20+). A single DLT, bilateral pulmonary emboli, occurred at 320 mg qd. Few treatment-related AEs occurred across the 3 cohorts (Table). PK/biomarker data is pending. Available FDG-PET results from measurements in 8 pts with 2–3 target lesions showed good baseline reproducibility in SUVpeak, SUVmean and SUVmax, with intra-subject CV of 3.6%, 7.2% and 9.3%, respectively. Conclusions: Brivanib in combination with full-dose cetuximab was well tolerated at ≤800 mg qd and did not result in enhancement of cetuximab associated AEs. Pre-treatment FDG-PET is a highly reproducible imaging modality. [Table: see text] [Table: see text]

scholarly journals A phase I dose escalation study of a pharmacobiologically based scheduling of capecitabine and mitomycin C in patients with gastrointestinal malignancies

2009 ◽  
Vol 65 (5) ◽  
pp. 863-869
Author(s):  
Tanios Bekaii-Saab ◽  
Marisa Hill ◽  
Angela Campbell ◽  
Kavitha Kosuri ◽  
James Thomas ◽  
...  
Keyword(s):  
Phase I ◽  
Mitomycin C ◽  
Dose Escalation ◽  
Dose Escalation Study ◽  
Gastrointestinal Malignancies
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