title: Devising two-stage and multistage phase II studies on systemic adjuvant therapy for uveal melanoma.
abstract: OBJECTIVE
  Almost all uveal melanomas showing chromosome 3 loss (i.e., monosomy 3) are fatal. Randomized clinical trials are therefore needed to evaluate various systemic adjuvant therapies. Conventional trial designs require large numbers of patients, which are difficult to achieve in a rare disease. The aim of this study was to use existing data to estimate how sample size and study duration could be reduced by selecting high-risk patients and adopting multistage trial designs.
  
  
  METHODS
  We identified 217 patients with a monosomy 3 melanoma exceeding 15 mm in basal diameter; these patients had a median survival of 3.27 years. Several trial designs comparing overall survival were explored for such a population. A power of 0.90 to detect a hazard ratio of 0.737 was set, and recruitment of 16 patients per month was assumed.
  
  
  RESULTS
  A suitable single-stage study would require 960 patients and a duration of 76 months. A two-stage design with an interim analysis based on 852 patients after 53.3 months would have a 50% probability of stopping because no statistically significant treatment effect is seen. Encouraging but inconclusive results would require a further 108 patients and prolongation of the study to 77.2 months. A multistage design would have a 43% probability of stopping before 47 months having recruited 759 patients.
  
  
  CONCLUSIONS
  Prospects for clinical studies of systemic adjuvant therapy for uveal melanoma are enhanced by multistage trial designs enrolling only high-risk patients.
authors: Medical and Pharmaceutical Statistics Research Unit, Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom. j.whitehead@lancaster.ac.uk
authors: John
authors: J
authors: Whitehead
authors: Svetlana
authors: S
authors: Tishkovskaya
authors: Jemma
authors: J
authors: O'Connor
authors: Bertil
authors: B
authors: Damato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D018401:Sample Size; D014604:Uveal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents