Entry Detail
| General information | |
| Database: | DB00371 |
| Objective: | The primary objective was demonstration of improvement in progression free survival (PFS) with vandetanib compared with placebo. |
| Authors: | Thornton K, et al |
| Title: | Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary. |
| Journal: | Clin Cancer Res. |
| Year: | 2012 |
| PMID: | 22665903 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | vandetanib |
| Target: | Epidermal growth factor receptor Vascular endothelial growth factor receptor 2 Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | thyroid cancer |
| Cancer Subtype: | medullary thyroid carcinoma. |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | doubleblind, randomized, placebocontrolledphase III trial |
| Key Patients Feature: | medullary thyroid carcinoma. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | A: vandetanib B: placebo |
| Treatment Info: | Patients were randomized 2:1 to vandetanib, 300 mg/d orally (n = 231), or to placebo (n = 100). |
| Primary End Point: | improvement in PFS with vandetanib compared with placebo. |
| Secondary End Point: | overall survival and objective response rate. |
| Patients Number: | 431 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | The objective response rate for patients randomized to vandetanib was 44% compared with 1% for patients randomized to placebo. All objective responses were partial responses. The median duration of response for patients treated with vandetanib was not reached. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median PFS was not reached for the vandetanib arm, compared with a 16month median PFS for the placebo arm |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common grade 3 and 4 toxicities (>5%) were diarrhea and/or colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash, and corrected QT interval (QTc) prolongation. |
| Conclusions: | Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the vandetanib Risk Evaluation Mitigation Strategy Program are able to prescribe and dispense vandetanib. Treatmentrelated risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease. |