Entry Detail
| General information | |
| Database: | DB00372 |
| Objective: | There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a oncedaily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC. |
| Authors: | wells SA Jr, et al |
| Title: | Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, doubleblindphase III trial. |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22025146 |
| Trial Design | |
| Clinical Trial Id: | NCT00410761 |
| Agent: | vandetanib |
| Target: | Epidermal growth factor receptor Vascular endothelial growth factor receptor 2 Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | thyroid cancer |
| Cancer Subtype: | advanced medullary thyroid carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | multicenterphase III study¡¡ Randomized, DoubleBlindPhase III Trial |
| Key Patients Feature: | Eligible patients were adults who had measurable, unresectable locallyadvanced or metastatic, hereditary or sporadic MTC. Submission of a tumorsample was required except for patients with hereditary MTC who had adocumented germlineRET mutation. Other key inclusion criteria were WHOperformance status of 0 to 2 and serum calcitonin level 500 pg/mL. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A: vandetanib B: placebo |
| Treatment Info: | Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive openlabel vandetanib. |
| Primary End Point: | PFS |
| Secondary End Point: | objective response rate, disease control rate, and biochemical response. |
| Patients Number: | 331 |
| Trial Results | |
| DLT_MTD: | Common adverse events (anygrade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56%v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26%v 9%). |
| Objective Response Rate: | Statistically significant advantages for vandetanib were also seen forobjective response rate (P .001), disease control rate (P .001), and biochemical response (P .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). |
| Disease Control Rate: | 87% for vandetanib group and 71 for placebo group. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 19.3 months in the placebo group and not reached for the vandetanib group. (HR, 0.46; 95% CI, 0.31 to 0.69; P=0 .001) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%). |
| Conclusions: | Vandetanib demonstrated therapeutic efficacy in aphase III trial of patients with advanced MTC (ClinicalTrials.govNCT00410761). |