Entry Detail
| General information | |
| Database: | DB00373 |
| Objective: | There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET protooncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This openlabel, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC |
| Authors: | wells SA Jr, et al |
| Title: | Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20065189 |
| 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: | openlabel, phase II study conducted at seven centers |
| Key Patients Feature: | Adult patients who had unresectable, locally advanced or metastaticMTC with a confirmed clinical diagnosis of MEN2A, MEN2B, or FMTC and agermlineRET mutation were eligible. Other key inclusion criteria included thepresence of at least one measurable lesion according to Response EvaluationCriteria in Solid Tumors (RECIST) guidelines14; WHO performance status of0 to 2; and adequate cardiac, hematopoietic, hepatic, and renal function.Patients with brain metastases were eligible if were treated with radiationtherapy at least 4 weeks before entry and were clinically stable without corticosteroid treatment for 1 week. Patients were ineligible if they had receivedprior chemotherapy and/or radiation therapy within 4 weeks before the initi¡¡ation of the study therapy |
| Biomarker: | serum levels of thepolypeptide, calcitonin, and the glycoprotein, carcinoembryonic antigen(CEA), which are secreted by MTC cells |
| Biomark Analysis: | In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. |
| Control Group Info: | single arm |
| Treatment Info: | Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with oncedaily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. |
| Primary End Point: | objective tumor response; |
| Secondary End Point: | the duration of response; disease control;PFS; safety and tolerability; and changes in serum levels of the polypeptide, calcitonin, and the glycoprotein, carcinoembryonic antigen(CEA) |
| Patients Number: | 30 |
| Trial Results | |
| DLT_MTD: | The most common adverse events werediarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). |
| Objective Response Rate: | a confirmed objectivepartial response was achieved in six patients (20%). The medianduration of response at data cutoff was 10.2 months (range, 1.9 to 16.9months; 95% CI, 8.0 to 13.2 months), and three patients developedprogressive disease subsequent to confirmation (one each at 10.6months, 27.3 months, and 27.9 months). Durable stable disease (disease that was stable for 24 weeks) was reported in 16 patients(53%). |
| Disease Control Rate: | 0.73 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 27.9 months (95% CI, 19.4 to not estimable) |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). |
| Conclusions: | In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy. |