title: Challenges in initiating and conducting personalized cancer therapy trials: perspectives from WINTHER, a Worldwide Innovative Network (WIN) Consortium trial.
abstract: Advances in 'omics' technology and targeted therapeutic molecules are together driving the incorporation of molecular-based diagnostics into the care of patients with cancer. There is an urgent need to assess the efficacy of therapy determined by molecular matching of patients with particular targeted therapies. WINTHER is a clinical trial that uses cutting edge genomic and transcriptomic assays to guide treatment decisions. Through the lens of this ambitious multinational trial (five countries, six sites) coordinated by the Worldwide Innovative Networking Consortium for personalized cancer therapy, we discovered key challenges in initiation and conduct of a prospective, omically driven study. To date, the time from study concept to activation has varied between 19 months at Gustave Roussy Cancer Campus in France to 30 months at the Segal Cancer Center, McGill University (Canada). It took 3+ years to be able to activate US sites due to national regulatory hurdles. Access to medications proposed by the molecular analysis remains a major challenge, since their availability through active clinical trials is highly variable over time within sites and across the network. Rules regarding the off-label use of drugs, or drugs not yet approved at all in some countries, pose a further challenge, and many biopharmaceutical companies lack a simple internal mechanism to supply the drugs even if they wish to do so. These various obstacles should be addressed to test and then implement precision medicine in cancer.
authors.affiliation: Vall D'Hebron Institute of Oncology and Universitat Autonoma de Barcelona, Barcelona, Spain jrodon@vhio.net.
authors.forename: J
authors.initials: J
authors.lastname: Rodon
authors.affiliation: Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Oncology Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.affiliation: Segal Cancer Center, Jewish General Hospital Mcgill University, Montreal Quebec Consortium de Recherche en Oncologie Clinique, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Batist
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: A
authors.initials: A
authors.lastname: Tsimberidou
authors.affiliation: WIN Consortium, Villejuif, France.
authors.forename: C
authors.initials: C
authors.lastname: Bresson
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: The National Institute of Biotechnology in the Negev, Ben Gurion University, Beer-Sheva, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Rubin
authors.affiliation: Oncology Institute, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Onn
authors.affiliation: American Society of Clinical Oncology (ASCO), Alexandria.
authors.forename: R L
authors.initials: RL
authors.lastname: Schilsky
authors.affiliation: Segal Cancer Center, Jewish General Hospital Mcgill University, Montreal Quebec Consortium de Recherche en Oncologie Clinique, Quebec, Canada.
authors.forename: W H
authors.initials: WH
authors.lastname: Miller
authors.affiliation: Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
authors.forename: A M
authors.initials: AM
authors.lastname: Eggermont
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: J
authors.initials: J
authors.lastname: Mendelsohn
authors.affiliation: Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
authors.forename: V
authors.initials: V
authors.lastname: Lazar
authors.affiliation: Center for Personalized Cancer Therapy, UC San Diego-Moores Cancer Center, La Jolla, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000970:Antineoplastic Agents / Q000191:economics / Q000600:supply & distribution / Q000627:therapeutic use*; D002170:Canada; D002986:Clinical Trials as Topic / Q000191:economics / Q000331:legislation & jurisprudence / Q000379:methods*; D005602:France; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007557:Israel; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D057285:Precision Medicine / Q000379:methods*; D011446:Prospective Studies; D013030:Spain; D014481:United States
chemical_list: D000970:Antineoplastic Agents
keywords: biomarker; clinical trials; personalized cancer therapy