title: Adaptive seamless design for an efficacy trial of replication-competent adenovirus-mediated suicide gene therapy and radiation in newly-diagnosed prostate cancer (ReCAP Trial).
abstract: OBJECTIVE
  Cumulative evidence has suggested investigation of the efficacy of Replication-Competent Adenovirus-mediated Suicide Gene Therapy in newly-diagnosed Prostate Cancer (ReCAP). There is a challenge in designing an efficacy trial for newly-diagnosed prostate cancer given its long natural history. The regulatory agency recommended a Phase II trial for safety before conducting the efficacy trial.
  
  
  METHODS
  The ReCAP trial is an adaptive seamless, multi-site open-label, randomized Phase II/III trial. Two hundred eighty men will be randomized to receive either replication-competent adenovirus-mediated suicide gene therapy followed by radiation (Arm 1) or radiation alone (Arm 2). Phase II trial component will include the first 21 patients in Arm 1 with complete toxicity through day 90 for safety evaluation. The primary efficacy endpoint is the time free from biochemical and/or clinical failure (FFF). The secondary efficacy endpoints are 2-year prostate biopsies and overall survival. Unequal spaced interim looks are proposed with the adaptive sample-size re-estimation.
  
  
  RESULTS
  This trial has been approved by the FDA for the study therapy investigation and is currently recruiting patients.
  
  
  CONCLUSIONS
  Challenges remain in designing newly-diagnosed prostate cancer trials. Adaptive seamless design is time-saving and a cost-effective design in the development of novel medical therapies, but requires a specified statistical plan in the decision process involved.
authors.affiliation: Department of Public Health Sciences, Henry Ford Health System, Detroit, MI 48202, USA. mlu1@hfhs.org
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Svend O
authors.initials: SO
authors.lastname: Freytag
authors.forename: Hans
authors.initials: H
authors.lastname: Stricker
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Kenneth
authors.initials: K
authors.lastname: Barton
authors.forename: Benjamin
authors.initials: B
authors.lastname: Movsas
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000502:physiology; D000963:Antimetabolites / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D003131:Combined Modality Therapy; D005437:Flucytosine / Q000627:therapeutic use; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D011788:Quality of Life; D050397:Radiotherapy, Intensity-Modulated; D018401:Sample Size; D016896:Treatment Outcome; D000077562:Valganciclovir; D014779:Virus Replication
chemical_list: D000963:Antimetabolites; D000998:Antiviral Agents; D005437:Flucytosine; D000077562:Valganciclovir; D015774:Ganciclovir