title: Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512.
abstract: BACKGROUND
  Sorafenib, a multikinase inhibitor of cell proliferation and angiogenesis, inhibits the mitogen-activated protein kinase pathway that is activated in most uveal melanoma tumors. This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP) in metastatic uveal melanoma.
  
  
  METHODS
  Twenty-five patients with stage IV uveal melanoma who had received 0-1 prior systemic therapy were enrolled. Treatment included up to 6 cycles of carboplatin (AUC = 6) and paclitaxel (225 mg/m(2)) administered IV on day 1 plus sorafenib (400 mg PO twice daily), followed by sorafenib monotherapy until disease progression. The primary endpoint was objective response rate (ORR); a two-stage design was used with the study to be terminated if no confirmed responses were observed in the first 20 evaluable patients. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  No confirmed objective responses occurred among the 24 evaluable patients (ORR = 0% [95% CI: 0-14%]) and the study was terminated at the first stage. Minor responses (tumor regression less than 30%) were seen in eleven of 24 (45%) patients. The median PFS was 4 months [95% CI: 1-6 months] and the 6-month PFS was 29% [95% CI: 13%-48%]. The median OS was 11 months [95% CI: 7-14 months].
  
  
  CONCLUSIONS
  In this study, the overall efficacy of CP plus sorafenib in metastatic uveal melanoma did not warrant further clinical testing when assessed by ORR, although minor tumor responses and stable disease were observed in some patients.
  
  
  BACKGROUND
  ClinicalTrials.govNCT00329641.
authors.affiliation: Medical Oncology, University of Washington, Seattle, WA, USA. sbhatia@uw.edu
authors.forename: Shailender
authors.initials: S
authors.lastname: Bhatia
authors.forename: James
authors.initials: J
authors.lastname: Moon
authors.forename: Kim A
authors.initials: KA
authors.lastname: Margolin
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Weber
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lao
authors.forename: Megan
authors.initials: M
authors.lastname: Othus
authors.forename: Ana M
authors.initials: AM
authors.lastname: Aparicio
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
authors.forename: Vernon K
authors.initials: VK
authors.lastname: Sondak
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D054316:Biomarkers, Pharmacological; D016190:Carboplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D017239:Paclitaxel / Q000008:administration & dosage; D010671:Phenylurea Compounds / Q000008:administration & dosage; D000077157:Sorafenib; D016896:Treatment Outcome; D014602:Uvea / Q000187:drug effects* / Q000473:pathology; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000098943:Uveal Melanoma
chemical_list: D054316:Biomarkers, Pharmacological; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D016190:Carboplatin; D017239:Paclitaxel