Entry Detail
| General information | |
| Database: | DB00176 |
| Objective: | The identification of somatic mutations in the gene encoding the serinethreonine protein kinase BRAF (BRAF) in the majority of melanomas offers an opportunity to test oncogenetargeted therapy for this disease. |
| Authors: | Flaherty KT, et al |
| Title: | Inhibition of mutated, activated BRAF in metastatic melanoma. |
| Journal: | N Engl J Med. |
| Year: | 2010 |
| PMID: | 20818844 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | vemurafenib |
| Target: | BRaf protooncogene serine/threonineprotein kinase |
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a multicenter, phase I, doseescalation trial |
| Key Patients Feature: | Eligibility criteria included the provision of written informed consent, an age of 18 years or older, solid tumors confirmed histologically that were refractory to standard therapy or for which standard or curative therapy did not exist |
| Biomarker: | BRAF mutated |
| Biomark Analysis: | In the doseescalation cohort, among the 16 patients with melanoma whose tumors carried the V600E BRAF mutation and who were receiving 240 mg or more of PLX4032 twice daily, 10 had a partial response and 1 had a complete response. |
| Control Group Info: | single arm |
| Treatment Info: | Patients received PLX4032 twice daily until they had disease progression. Pharmacokinetic analysis and tumorresponse assessments were conducted in all patients. In selected patients, tumor biopsy was performed before and during treatment to validate BRAF inhibition. |
| Primary End Point: | Pharmacokinetic analysis and tumorresponse assessments, PFS, |
| Secondary End Point: | NA |
| Patients Number: | 55 |
| Trial Results | |
| DLT_MTD: | The recommendedphase 2 dose was 960 mg twice daily, with increases in the dose limited by grade 2 or 3 rash, fatigue, and arthralgia. |
| Objective Response Rate: | In the doseescalation cohort, among the 16 patients with melanoma whose tumors carried the V600E BRAF mutation and who were receiving 240 mg or more of PLX4032 twice daily, 10 had a partial response and 1 had a complete response. Among the 32 patients in the extension cohort, 24 had a partial response and 2 had a complete response |
| Disease Control Rate: | as the former |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The estimated median progression free survival among all patients was more than 7 months. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | grade 2 or 3 rash, fatigue, and arthralgia |
| Conclusions: | Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients. |