http://clinicaltrials.gov/ct2/show/nct01462513



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Page 1 of 5 Home Search Study Topics Glossary Search Full Text View Tabular View No Study Results Posted Related Studies L-BLP25 in Patients With Colorectal Carcinoma After Curative Resection of Hepatic Metastases (LICC) This study is currently recruiting participants. Verified October 2011 by Johannes Gutenberg University Mainz First Received on October 27, 2011. Last Updated on February 2, 2012 History of Changes Sponsor: Dr. Carl Schimanski Information provided by (Responsible Party): Dr. Carl Schimanski, Johannes Gutenberg University Mainz ClinicalTrials.gov Identifier: NCT01462513 Purpose Comparative evaluation of recurrence-free survival time between the treatment groups (L-BLP25 plus cyclophosphamide versus placebo vaccination and saline infusion.) Condition Intervention Phase Colon Carcinoma Rectum Carcinoma Biological: L-BLP25 Biological: Placebo Phase II Study Type: Study Design: Official Title: Interventional Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment LICC: L-BLP25 in Patients With Colorectal Carcinoma After Curative Resection of Hepatic Metastases - a Randomized, Placebo-controlled, Multicenter, Multinational, Double Blinded Phase II Trial Resource links provided by NLM: MedlinePlus related topics: Cancer U.S. FDA Resources Further study details as provided by Johannes Gutenberg University Mainz: Primary Outcome Measures: Comparative evaluation of recurrence-free survival time between the treatment groups (L-BLP25 plus cyclophosphamide versus placebo vaccination and saline infusion) [ Designated as safety issue: No ] The primary variable of this trial is recurrence free survival (RFS) time. RFS time will be measured from the date of randomization to the date of recurrence. For subjects not known to have experienced recurrence or death at the time of analysis, the time between the date of randomization and the date of last evaluation for recurrence will be calculated and used as a censored observation in the analysis. Secondary Outcome Measures: Overall survival time [ Designated as safety issue: No ] Overall survival (OS) time of all and of of MUC1 positive cancers, respectively, will be measured from the date of randomization to the date of death. For subjects not known to be deceased at the time of analysis, the time between the date of randomization and the date of last contact, or date lost to follow-up, will be calculated and used as a censored observation in the analysis. Safety/tolerability [ Designated as safety issue: Yes ] Assessment of safety will include: AEs, SAEs Vital signs (body temperature, respiratory rate, heart rate, and blood pressure) and physical examinations, Clinical laboratory assessments from hematology and biochemistry samples

Page 2 of 5 Recurrence free survival time in a subgroup of MUC1 positive cancers [ Designated as safety issue: No ] Recurrence free survival (RFS) time of MUC1 positive cancers will be measured from the date of randomization to the date of relapse based on standard imaging. For subjects not known to have experienced recurrence or death at the time of analysis, the time between the date of randomization and the date of last evaluation for recurrence or death will be calculated and used as a censored observation in the analysis. Overall survival time in a subgroup of MUC1 positive cancers [ Designated as safety issue: No ] Overall survival (OS) time of MUC1 positive cancers will be measured from the date of randomization to the date of death. For subjects not known to be deceased at the time of analysis, the time between the date of randomization and the date of last contact, or date lost to follow-up, will be calculated and used as a censored observation in the analysis. Estimated Enrollment: 159 Study Start Date: August 2011 Estimated Study Completion Date: September 2017 Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure) Arms Experimental: L-BLP25 L-BLP25 vaccination Placebo Comparator: Placebo Placebo Assigned Interventions Biological: L-BLP25 Vaccination 930µg per vaccination once weekly for 8 weeks, then at 6- week intervals during years 1 and 2, at 12-week intervals during year 3 Other Name: MUC1-antibody Biological: Placebo Vaccination: Placebo 930µg per vaccination, once weekly for 8 weeks, then at 6-week intervals during years 1 and 2 and at 12-week intervals in year 3 Eligibility Detailed Description: This trial is designed for patients with metastatic colorectal carcinoma (CRC), who have undergone a complete resection of their primary tumor and recent resection of their liver metastases (R0 or R1) with curative intent. No generally accepted standard care is available following curative-intent resection of hepatic metastases in colorectal cancer patients. L-BLP25 is a cancer vaccine that targets MUC1, a well known tumor-associated antigen. Recently, it has been shown that MUC1 is associated with cellular transformation as demonstrated by tumorigenicity and can confer resistance to genotoxic agents. High levels of MUC1 cell surface expression, reported immunosuppressive activities of its released ectodomain, and anti-adhesive properties all contribute to the ability of the MUC1 antigen to protect and promote tumor cell growth and survival, and make MUC1 an attractive target for cancer immunotherapy. Based on these results, L BLP25 may have potential as adjuvant therapy after curative resection of hepatic metastases in colorectal cancer patients. Ages Eligible for Study: Genders Eligible for Study: Accepts Healthy Volunteers: 18 Years and older Both No Criteria Inclusion Criteria: Signed written informed consent. Female patients of childbearing potential (and if appropriate male patients with female partners of childbearing potential) must be willing to use an adequate method of contraception for 4 weeks prior to, during and 12 weeks after the last dose of trial medication. A negative pregnancy test is required for female subjects. Adequate contraception for female subjects is defined as two barrier methods, or one barrier method with a spermicide, or intrauterine device or use of hormonal female contraceptive. Histologically confirmed diagnosis of adenocarcinoma of the colon or rectum with complete resection of primary tumor and no evidence of local relapse. Metastatic disease of the liver, with recent (< 6 weeks prior to randomization) resection (R0 or R1) of all liver metastases. Metastasectomy may have been either synchronous or metachronous. Any neoadjuvant therapy may have been applied for maximal 3 months prior to metastasectomy. Subject has had a colonoscopy or rectoscopy within the last three months prior to initiation of therapy Subject has an ECOG performance status of 0 or 1. Subject has adequate hematologic, hepatic, and renal function within 2 weeks prior to initiation of therapy as defined by the following: Absolute neutrophils > 1,500/mm3 and platelets > 140,000/mm3. Bilirubin < 1.5 x upper limit of normal (ULN). AST and ALT < 2.5 x ULN. Creatinine < 1.5 x ULN. International Normalized Ratio (INR) and partial thromboplastin time (PTT) in the normal range of the local lab. Willingness to comply with study protocol requirements. Exclusion Criteria: Metastases other than liver metastases. R2 and Rx resected liver metastases. Patients with R1 resected liver metastases can be included if a further surgical resection is seen as not indicated or necessary in the surgeon s opinion. Chemotherapy within 4 weeks prior to randomization. Receipt of immunotherapy (e.g. interferons, tumor necrosis factor, interleukins, or growth factors [GM-CSF, G-

Page 3 of 5 CSF, M- CSF], monoclonal antibodies) within 4 weeks (28 days) prior to randomization. Any known autoimmune disease, past or current. A recognized immunodeficiency disease including cellular immuno-deficiencies, hypogammaglobulinemia or dysgammaglobulinemia; hereditary or congenital immunodeficiencies. Known or newly diagnosed active hepatitis B infection and/or hepatitis C infection, autoimmune hepatitis, known human immunodeficiency virus infection, or any other infectious process that in the opinion of the investigator could compromise the subject's ability to mount an immune response, or expose him/ her to likelihood of more and/or severe side effects. Past or current history of malignant neoplasm other than CRC, except for curatively treated non-melanoma skin cancer, in-situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least 5 years. Medical or psychiatric conditions that would interfere with ability to provide informed consent, communicate side effects, or comply with protocol requirements. Clinically significant cardiac disease, e.g. cardiac failure of New York Heart Association classes III-IV; uncontrolled angina pectoris, uncontrolled arrhythmia, uncontrolled hypertension, myocardial infarction in the previous 12 months as confirmed by an ECG. Splenectomy. Previous (less than 4 weeks prior to randomization) or concurrent treatment with a non-permitted drug. Pregnancy and lactation period. Participation in another clinical study within 30 days prior to randomization. Known hypersensitivity to the study treatment drugs. Known alcohol or drug abuse. Legal incapacity or limited legal capacity. Any other reason that, in the opinion of the investigator, precludes the subject from participating in this study. Contacts and Locations Please refer to this study by its ClinicalTrials.gov identifier: NCT01462513 Locations Austria LKH-Universitätsklinikum Graz Graz, Austria, 8036 Contact: Hellmut Samonigg, Prof. Dr. +4331638513115 hellmut.samonigg@medunigraz.at Principal Investigator: Hellmut Samonigg, Prof. Dr. Sub-Investigator: Michael Halm, MD Sub-Investigator: Martin Pichler, MD Sub-Investigator: Renate Schaberl-Moser, MD Salzburger Universitätsklinikum, Universitätsklinik für Innere Medizin III Salzburg, Austria, 5020 Contact: Richard Greil, Prof. Dr. +43 662 4482 2880 r.greil@salk.at Principal Investigator: Richard Greil, Prof. Dr. Sub-Investigator: Brigitte Mlineritsch, MD Germany Campus Virchow-Klinikum, Charite Centrum 8 Berlin, Germany, 13353 Contact: Daniel Seehofer, MD +49 30450552001 daniel.seehofer@charite.de Principal Investigator: Daniel Seehofer, MD Sub-Investigator: Roberta Bova, MD Sub-Investigator: Dennis Eurich, MD Sub-Investigator: Wladimir Faber, MD Sub-Investigator: Anja Kießling, MD Klinikum Dortmund ggmbh, Medizinische Klinik Mitte Dortmund, Germany, 44137 Contact: Michael Heike, Prof. Dr. +49 231 95321770 michael.heike@klinikumdo.de Principal Investigator: Michael Heike, Prof. Dr. Sub-Investigator: Sabine Bäumer, MD Sub-Investigator: Peter Boris Czyborra, MD Onkologische Gemeinschaftspraxis Dörfel & Göhler Dresden, Germany, 01127 Contact: Steffen Dörfel, Dipl. med. +49 351 849507141 doerfel@onkozentrum.de Principal Investigator: Steffen Dörfel, Dipl. med. Sub-Investigator: Thomas Göhler, MD Universitätsklinikum Essen WTZ-Ambulanz, Innere Medizin (Tumorforschung) Essen, Germany, 45122 Contact: Stefan Kasper, MD +49 201 72385062 stefan.kasper@uk-essen.de Principal Investigator: Stefan Kasper, MD Sub-Investigator: Marit Ahrens, MD Sub-Investigator: Jörg Hense, MD Sub-Investigator: Mathias Hoiczyl, MD Sub-Investigator: Johannes Meiler, MD Sub-Investigator: Mareike Tometten, MD Sub-Investigator: Martin Schuler, MD

Page 4 of 5 Klinikum der Johann W- Goethe Unversität, Klinik für Allgemein- und Viszeralchirurgie Frankfurt, Germany, 60590 Contact: Wolf O Bechstein, Professor +49 69 63015251 wolf.bechstein@kgu.de Principal Investigator: Wolf O Bechstein, Professor Sub-Investigator: Christiane Gog, MD Sub-Investigator: Angelika Mertens, MD Sub-Investigator: Christiane Mönch, MD Sub-Investigator: Jörg Trojan, Professor Onkologische Schwerpunktpraxis Eppendorf Hamburg, Germany, 20249 Contact: Susanna Hegewisch-Becker, Prof. Dr. +49 40 4602001 hegewisch@onkologie-eppendorf.de Principal Investigator: Susanna Hegewisch-Becker, Prof. Dr. Sub-Investigator: Thorsten Dierlamm, MD Städtisches Klinikium Abt. Allgemein- und Visceralchirurgie Karlsruhe, Germany, 76133 Contact: Michael Schön, Professor +49 721 9742101 michael.schoen@klinikum-karlsruhe.de Principal Investigator: Michael Schön, Professor Sub-Investigator: Daniel Gärtner, MD Sub-Investigator: Monika Harbrecht-Hessle, MD Universitätsmedizin Mainz Mainz, Germany, 55131 Contact: Carl C Schimanski, MD +49 6131 176076 schimanski@1-med.klinik.uni-mainz.de Contact: Markus Möhler, MD +49 6131 175712 markus.moehler@unimedizin-mainz.de Principal Investigator: Carl C Schimanski, MD Sub-Investigator: Tina Friesing-Sosnik, MD Sub-Investigator: Markus Möhler, MD Sub-Investigator: Julia Sieg, MD Sub-Investigator: Daniel Foltys, MD Sub-Investigator: Marcus A. Wörns, MD Sub-Investigator: Michael Heise, MD Praxis für Hämatologie und Onkologie Mülheim an der Ruhr, Germany, 45468 Contact: Jan Schröder, PD Dr. med. +49 208 76981 jan.schroeder@onkologie-mh.de Principal Investigator: Jan Schröder, PD Dr. med. Sub-Investigator: Katharina Sieg, MD Klinikum der Universität München-Grosshadern, Medizinische Klinik III München, Germany, 81377 Contact: Volker Heinemann, Professor +49 89 70953019 Volker.Heinemann@med.uni-muenchen.de Principal Investigator: Volker Heinemann, Professor Sub-Investigator: Roswitha Forstpointer, MD Sub-Investigator: Clemens Gießen, MD Sub-Investigator: Dominik Modest, MD Sub-Investigator: Sebastian Stinzing, MD GP für Hämatologie und Onkologie Offenburg Offenburg, Germany, 77654 Contact: Bernhard Linz, MD +49 781 9705779 linz@onkologie-offenburg.de Principal Investigator: Bernhard Linz, MD Sub-Investigator: Andreas Jakob, MD Sub-Investigator: Marianne Müller, MD Oncologianova GmbH Recklinghausen, Germany, 45657 Contact: Friedrich Overkamp, MD +49 2361 90427 23 overkamp@onkologie-re.de Principal Investigator: Friedrich Overkamp, MD Sub-Investigator: Ludger Heflik, MD Sub-Investigator: Till-Oliver Emde Leopoldina Krankenhaus Schweinfurt, Germany, 97422 Contact: Stephan Kanzler, Prof. Dr. +49 9721 7200 skanzler@leopoldina.de Principal Investigator: Stephan Kanzler, Prof. Dr. Sub-Investigator: Hans Reinel, MD Sub-Investigator: Andrea Buwe Robert-Bosch Krankenhaus, Zentrum für Innere Medizin Stuttgart, Germany, 70376 Contact: Matthias Vöhringer, MD +49 711 81013506 matthias.voehringer@rbk.de Principal Investigator: Matthias Vöhringer, MD Sub-Investigator: Walter-Erich Aulitzky, Professor Sub-Investigator: Liza Bacchus-Gerybadze, MD Sub-Investigator: Martin Kaufmann, MD Sub-Investigator: Sonja Martin, MD Sub-Investigator: Annette Steckkönig, MD Universitätsklinikum, Zentrum für Innere Medizin Ulm, Germany, 89081 Contact: Götz von Wichert, Professor +49 731 50044508 goetz.wichert@uniklinik-ulm.de Principal Investigator: Götz von Wichert, Professor Sub-Investigator: Johann Ahn, MD Sub-Investigator: Angelika Kestler, MD Sub-Investigator: Jochen Kraus, MD Sub-Investigator: Sven Walter, MD Sub-Investigator: Eugen Zizer, MD

Page 5 of 5 Sponsors and Collaborators Dr. Carl Schimanski Investigators Klinikum Weiden, Medizinische Klinik I Weiden, Germany, 92637 Contact: Frank Kullmann, Professor +49 961 3033114 frank.kullmann@kliniken-nordoberpfalz.ag Principal Investigator: Frank Kullmann, Professor Sub-Investigator: Armin Leitner, MD Sub-Investigator: Carsten Schwab, MD Sub-Investigator: Holger Tuchbreiter, MD Principal Investigator: Carl Christoph Schimanski, MD Universitätsmedizin Mainz More Information No publications provided Responsible Party: Dr. Carl Schimanski, Coordinating Investigator, Johannes Gutenberg University Mainz ClinicalTrials.gov Identifier: NCT01462513 History of Changes Other Study ID Numbers: LICC01 Study First Received: October 27, 2011 Last Updated: February 2, 2012 Health Authority: Germany: Paul-Ehrlich-Institut; Austria: Federal Office for Safety in Health Care Keywords provided by Johannes Gutenberg University Mainz: Colon carcinoma Rectum carcinoma Liver metastases Additional relevant MeSH terms: Carcinoma Colorectal Neoplasms Neoplasm Metastasis Rectal Neoplasms Liver Neoplasms Colonic Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Neoplastic Processes Pathologic Processes Liver Diseases ClinicalTrials.gov processed this record on February 14, 2012 Contact Help Desk Lister Hill National Center for Biomedical Communications, U.S. National Library of Medicine, U.S. National Institutes of Health, U.S. Department of Health & Human Services, USA.gov, Copyright, Privacy, Accessibility, Freedom of Information Act