Repeatability of 18F-FDG PET in a Multicenter Phase I Study of Patients with Advanced Gastrointestinal Malignancies

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]

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Six-month results of the Multicenter Phase I Study of Excimer Laser Myopic Keratomileusis

Journal of Cataract & Refractive Surgery ◽

10.1016/s0886-3350(13)80648-7 ◽

1994 ◽

Vol 20 (6) ◽

pp. 610-615 ◽

Cited By ~ 43

Author(s):

Stephen F. Brint ◽

Michael D. Ostrick ◽

Coni Fisher ◽

Stephen G. Slade ◽

Robert K. Maloney ◽

...

Keyword(s):

Phase I ◽

Excimer Laser ◽

Phase I Study ◽

Multicenter Phase

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A Multicenter Phase I Study of Pazopanib in Combination with Paclitaxel in First-Line Treatment of Patients with Advanced Solid Tumors

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-14-0431 ◽

2014 ◽

Vol 14 (2) ◽

pp. 461-469 ◽

Cited By ~ 20

Author(s):

Kari L. Kendra ◽

Ruth Plummer ◽

Ravi Salgia ◽

Mary E. R. O'Brien ◽

Elaine M. Paul ◽

...

Keyword(s):

Phase I ◽

Solid Tumors ◽

Phase I Study ◽

Advanced Solid Tumors ◽

Line Treatment ◽

First Line ◽

Multicenter Phase ◽

First Line Treatment

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Chemoradiotherapy with temozolomide after high-dose methotrexate for primary CNS lymphoma: a multicenter phase I study of a response-adapted strategy

Annals of Hematology ◽

10.1007/s00277-020-04220-1 ◽

2020 ◽

Vol 99 (10) ◽

pp. 2367-2375

Author(s):

Silvia Chiesa ◽

Stefan Hohaus ◽

Lorenzo Falcinelli ◽

Francesco D’Alò ◽

Massimo Fabrizio Martelli ◽

...

Keyword(s):

Phase I ◽

Phase I Study ◽

Primary Cns Lymphoma ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Methotrexate ◽

Multicenter Phase ◽

Dose Methotrexate

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Biweekly oxaliplatin with gemcitabine and capecitabine in advanced gastrointestinal malignancies: A phase I study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4560 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4560-4560

Author(s):

B. R. Tan ◽

W. S. Brenner ◽

J. Picus ◽

R. Suresh ◽

S. Sorcher ◽

...

Keyword(s):

Phase I ◽

Phase I Study ◽

Maximum Tolerated Dose ◽

Toxicity Assessment ◽

Unknown Primary ◽

Pharmacokinetic Studies ◽

Gastrointestinal Malignancies ◽

Constant Rate ◽

Grade 3 ◽

Triplet Regimen

4560 Background: Oxaliplatin (OX), gemcitabine (GEM) and capecitabine (CAP) are all active agents against various gastrointestinal and other malignancies and have different mechanisms of action and toxicity profiles. This Phase I study aims to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) associated with this triplet regimen. Methods: The modified Fibonacchi 3/cohort dose escalation schema was used to determine the MTD and DLT of OX, GEM and CAP. Oxalipaltin [85–100 mg/m2] IV over 2 hours and gemcitabine [800–1,000 mg/m2] were given at a constant rate infusion of 10 mg/m2/min on days 1 & 15, while CAP [600–800 mg/m2] was given PO BID on days 1–7 and 15–21. 1 cycle = 28 days. Pharmacogenomic correlates including ERCC2, GSTP1, TYMS, TS del and TSER G>C were also obtained. A structured neurological toxicity assessment and questionnaire was also performed. Once MTD was established, additional patients were treated at the MTD and pharmacokinetic studies were performed on these additional patients. Results: 30 patients (M:F 2:1; 23% non-caucasian) with median age of 62 (range: 38–78) and PS of 0–1 were enrolled from 3/05 to 8/06. All patients had advanced GI malignancies (19 pancreatic, 6 biliary, 2 duodenal, 1 gastric, 1 esophageal, 1 GI unknown primary). Dose levels, # patients, DLT and best responses are tabulated below. Conclusions: The MTD of this triplet regimen is OX at 100 mg/m2, GEM at 800 mg/m2 days 1 & 15 with CAP at 800 mg/m2 PO BID days 1–7, 15–21. DLTs for this regimen include grade 3 fatigue and dyspnea as well as Grade 4 thrombocytopenia. CR is achieved in 2 patients (cholangiocarcinoma and pancreatic), while a patient with a GI unknown primary achieved PR. Several patients with pancreatic cancer achieved prolonged SD. An exploration of any association of toxicities and response with pharmacogenomic correlates is ongoing. A Phase II study in patients with pancreaticobiliary cancers is planned. This study is supported by Sanofi-Aventis Pharmaceuticals. [Table: see text] [Table: see text]

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