title: A prospective, non-randomized phase II trial of Trastuzumab and Capecitabine in patients with HER2 expressing metastasized pancreatic cancer.
abstract: BACKGROUND
  Pancreatic cancer is the fourth most common cause of cancer related death in Western countries. Advantages in surgical techniques, radiation and chemotherapy had almost no impact on the long term survival of affected patients. Therefore, the need for better treatment strategies is urgent. HER2, a receptor tyrosine kinase of the EGFR family, involved in signal transduction pathways leading to cell growth and differentiation is overexpressed in a number of cancers, including breast and pancreatic cancer. While in breast cancer HER2 has already been successfully used as a treatment target, there are only limited data evaluating the effects of inhibiting HER2 tyrosine kinases in patients with pancreatic cancer.
  
  
  METHODS
  Here we report the design of a prospective, non-randomized multi-centered Phase II clinical study evaluating the effects of the Fluoropyrimidine-carbamate Capecitabine (Xeloda) and the monoclonal anti-HER2 antibody Trastuzumab (Herceptin) in patients with non-resectable, HER2 overexpressing pancreatic cancer. Patients eligible for the study will receive Trastuzumab infusions on day 1, 8 and 15 concomitant to the oral intake of Capecitabine from day 1 to day 14 of each three week cycle. Cycles will be repeated until tumor progression. A total of 37 patients will be enrolled with an interim analysis after 23 patients.
  
  
  CONCLUSIONS
  Primary end point of the study is to determine the progression free survival after 12 weeks of bimodal treatment with the chemotherapeutic agent Capecitabine and the anti-HER2 antibody Trastuzumab. Secondary end points include patient's survival, toxicity analysis, quality of life, the correlation of HER2 overexpression and clinical response to Trastuzumab treatment and, finally, the correlation of CA19-9 plasma levels and progression free intervals.
authors.affiliation: Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg and Klinikum rechts der Isar, Technische Universität Munich, Ismaninger Strasse 22, 81675 Munich, Germany. Mihaljevic@chir.med.tu-muenchen.de
authors.forename: Andre
authors.initials: A
authors.lastname: Mihaljevic
authors.forename: Peter
authors.initials: P
authors.lastname: Büchler
authors.forename: Jan
authors.initials: J
authors.lastname: Harder
authors.forename: Ralf
authors.initials: R
authors.lastname: Hofheinz
authors.forename: Michael
authors.initials: M
authors.lastname: Gregor
authors.forename: Stephan
authors.initials: S
authors.lastname: Kanzler
authors.forename: Wolff
authors.initials: W
authors.lastname: Schmiegel
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.forename: Esther
authors.initials: E
authors.lastname: Endlicher
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
authors.forename: Thomas
authors.initials: T
authors.lastname: Seufferlein
authors.forename: Michael
authors.initials: M
authors.lastname: Geissler
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D017322:Clinical Trials, Phase II as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D015337:Multicenter Studies as Topic; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D012107:Research Design; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069287:Capecitabine; D003841:Deoxycytidine; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab