| General information |
| Database: | DB00400 |
| Objective: | SU5416 is a novel small organic molecule that noncompetitively inhibits the phosphorylation of the VEGF tyrosine kinase receptor, Flk1. Thisphase IB study was performed to determine the safety, pharmacokinetics, and preliminary efficacy of the combination of SU5416 and paclitaxel in recurrent or metastatic carcinoma of the head and neck. |
| Authors: | Cooney MM, et al |
| Title: | a phase IB clinical and pharmacokinetic study of the angiogenesis inhibitor SU5416 and paclitaxel in recurrent or metastatic carcinoma of the head and neck. |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2005 |
| PMID: | 15538570 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | SU5416
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | SU5416 and paclitaxel |
| Study Type: | phase IB clinical and pharmacokinetic study |
| Key Patients Feature: | Patients with histologically verified metastatic orlocoregionally recurrent squamous and nonsquamouscancer of the head and neck that was incurable bysurgery or radiation therapy were included. Only patientsolder than 18 years with an ECOG performance status¡ê 2 and a life expectancy of at least 12 weeks were eligible. Adequate hematologic (WBC >3500/ll, platelets>100, 000/ll, and hemoglobin >9.0 g/dl), renal (serumcreatinine <1.5 mg/dl), hepatic (bilirubin <1.5 mg/dl, and AST and ALT less than two times normal), andprothrombin time (PT) and partial thromboplastin time(PTT) within normal limits were required for eligibility |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Six patients received intravenous SU5416 110 mg/m2 on days 1, 15, 18, 22 and 25, and paclitaxel 70 mg/m2 on days 8, 15 and 22. Since two patients experienced a doselimiting toxicity (DLT) in cohort 1, the next six patients received identical treatment as above except the paclitaxel dose was reduced to 55 mg/m2 per week. |
| Primary End Point: | safety, pharmacokinetics, and preliminary efficacy |
| Secondary End Point: | NA |
| Patients Number: | 12 |
| Trial Results |
| DLT_MTD: | maximum tolerateddose of 145 mg/m2 per week; doselimiting toxicity(DLT) consisted of projectile vomiting and headache at190 mg/m2 [14] |
| Objective Response Rate: | Of the 12 patients enrolled in the study, 11 were evaluablefor response. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Most of the other toxicities seen were grade 1 or 2 in nature and consisted of headache, facial flushing, and fatigue. Two patients developed extensive ulcerative cavities at sites of prior radiation. |
| Conclusions: | The combination of SU5416 with paclitaxel had a higher than expected incidence of thromboembolic events and prophylactic anticoagulation should be considered for future trials that combine an angiogenesis inhibitor with cytotoxic chemotherapy. Although the future development of SU5416 as a chemotherapeutic agent is unclear, there was a clinical benefit seen with this combination in 36% of the patients. This trial supports the use of developing antiangiogenic combinations, using molecular targeted agents, in head and neck carcinoma. |