title: Lapatinib-capecitabine versus capecitabine alone as radiosensitizers in RAS wild-type resectable rectal cancer, an adaptive randomized phase II trial (LaRRC trial): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Preoperative radiochemotherapy followed by surgical removal of the rectum with total mesorectum excision is the preferred treatment option for stages II and III rectal cancer. However, development of metastatic disease is the main cause of death for these patients with 5-year disease-free survival rates of 56 %. Anti-epidermal growth factor receptor (EGFR) targeted therapy is effective in metastatic rectal cancer, and human epidermal growth factor receptor 2 (HER-2) signaling may mediate resistance to EGFR inhibitors. Moreover, preclinical data support a synergistic effect of EGFR inhibition with radiation therapy.
  
  
  METHODS
  This Bayesian phase II trial with adaptive randomization was designed to assess the efficacy of adding lapatinib, a dual inhibitor of EGFR and HER-2, to standard radiochemotherapy with capecitabine in stages II and III rectal cancer.
  
  
  CONCLUSIONS
  The results of this trial will provide evidence of the feasibility and efficacy of the combination of lapatinib-capecitabine as radiosensitizers and explore potential predictive biomarkers for response to this novel neoadjuvant approach to resectable rectal cancer.
  
  
  BACKGROUND
  EudraCT 2013-001203-36 . Registered on 13 December 2013.
authors.affiliation: Medical Oncology Department, IPO Porto FG, EPE, Rua António Bernardino de Almeida, 4200-072, Porto, Portugal. nuno.sousa@ipoporto.min-saude.pt.
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.affiliation: Radioncology Department, IPO Porto FG, EPE, Rua António Bernardino de Almeida, 4200-072, Porto, Portugal.
authors.forename: Olga
authors.initials: O
authors.lastname: Sousa
authors.affiliation: Surgical Oncology Department, IPO Porto FG, EPE, Rua António Bernardino de Almeida, 4200-072, Porto, Portugal.
authors.forename: Lúcio Lara
authors.initials: LL
authors.lastname: Santos
authors.affiliation: Department of Pathology, IPO Porto FG, EPE, Rua António Bernardino de Almeida, 4200-072, Porto, Portugal.|Department of Pathology and Molecular Immunology, Abel Salazar Institute of Biomedical Sciences - University of Porto, Rua de Jorge Viterbo Ferreira, no. 228, 4050-313, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.affiliation: Genetics Department, IPO Porto FG, EPE, Rua António Bernardino de Almeida, 4200-072, Porto, Portugal.|Biomedical Sciences Institute Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.affiliation: Gastroenterology Department, IPO Porto FG, EPE, Rua António Bernardino de Almeida, 4200-072, Porto, Portugal.|CINTESIS - Center for Health Technology and Services Research, Centro de Investigação Médica, Faculdade de Medicina da Universidade do Porto, Rua Dr. Plácido da Costa, s/n, 4200-450, Porto, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Dinis-Ribeiro
authors.affiliation: Screening and Test Evaluation Program (STEP), Sydney School of Public Health, The University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: Armando
authors.initials: A
authors.lastname: Teixeira-Pinto
keywords: Bayesian adaptive randomization; Capecitabine (capecitabine [supplementary concept]); Clinical trial; Lapatinib (lapatinib [supplementary concept]); Neoadjuvant therapy; Phase II; Radiotherapy; Randomized adaptive trial; Rectal neoplasms