Gemcitabine and Sorafenib in Advanced Biliary Tract Cancer (GEMSO) - Full Text View

Sponsors and Collaborators:	Johannes Gutenberg University Mainz Johannes Gutenberg University Mainz, interdisciplinary Center Clinical Trials
Information provided by:	Johannes Gutenberg University Mainz
ClinicalTrials.gov Identifier:	NCT00661830

Purpose

This trial will be conducted to evaluate the efficacy, safety and tolerability of a combination of gemcitabine plus sorafenib in comparison of gemcitabine plus placebo as a first-line palliative therapy in chemo-naive advanced or metastatic CCC. There is strong scientific rationale for exploring the role of sorafenib in combination with gemcitabine in advanced CCC.

Sorafenib is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGF-R2, R3 and PDGFR-β.

Mutations in these signaling pathways display by far the most common genetic alterations in CCC and overexpression correlates to poor prognosis. Furthermore, there is no evidence of a consistent or meaningful pharmacokinetic interaction between sorafenib and gemcitabine, suggesting that sorafenib can safely be combined with gemcitabine.

Clinical results of a combination of sorafenib and gemcitabine in a phase I study in pancreatic cancer suggested a therapeutic effect, and the safety and efficacy results together with the knowledge of the molecular pathology of CCC provide a rationale for a randomized, placebo-controlled phase II trial consisting of gemcitabine plus sorafenib in advanced CCC.

Condition	Intervention	Phase
Adenocarcinoma	Drug: Gemcitabine + Sorafenib Drug: Gemcitabine + Placebo	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Gemcitabine hydrochloride Gemcitabine Sorafenib Sorafenib tosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Randomized, Double-Blind, Multicenter Phase II Trial With Gemcitabine Plus Sorafenib Versus Gemcitabine Plus Placebo in Patients With Chemo-Naive Advanced or Metastatic Adenocarcinoma of the Biliary Tract

Further study details as provided by Johannes Gutenberg University Mainz:

Primary Outcome Measures:

Progression-free survival (PFS) [ Time Frame: one year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety and tolerability of a combination therapy [ Time Frame: ongoing ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	96
Study Start Date:	May 2008
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Gemcitabine + Sorafenib	Drug: Gemcitabine + Sorafenib Sorafenib 400 mg bid orally continuously Gemcitabine 1000 mg/m2 body surface i.v. first cycle at day 1, 8, 15, 22, 29, 36, 43. Next cycles at day 1, 8, 15.
2: Placebo Comparator Gemcitabine + Placebo	Drug: Gemcitabine + Placebo Gemcitabine 1000 mg/m2 body surface i.v. first cycle at day 1, 8, 15, 22, 29, 36, 43. Next cycles at day 1, 8, 15.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female patients aged 18 years and older
Signed and dated informed consent before the start of specific protocol procedures
Adenocarcinoma of the gallbladder or intrahepatic bile ducts or histologically proven hepatic metastases of an earlier resected and histologically proven biliary tract cancer
- Not amenable to curative surgical resection
- With at least one unidimensionally measurable target lesion in non-irradiated (or treated by photodynamic therapy, PDT) area (largest diameter ≥ 1 cm (spiral CT scan or MRI) or ≥ 2 cm (conventional CT scan)
- With pain and biliary obstruction controlled
- Cytologically or histologically confirmed
Note : in case of uncertain biliary tract origin (e.g., intrahepatic CCCs), inclusion is possible if
1. extensive search for primary tumor (thoracic and abdomino pelvic CT scan, colonoscopy, upper digestive endoscopy, serum PSA level for men or mammography for women, and FDG-PET if possible) is negative
2. histological examination is consistent with bile duct adenocarcinoma, with IHC positive for cytokeratin 7 and 19 and negative for cytokeratin 20 [Shimonishi, 2000].
3. No histological evidence of hepatocellular carcinoma (HCC)
4. No prior palliative (radio)-chemotherapy (gemcitabine or fluoropyrimidine-based chemotherapy)
Note:
1. previous adjuvant chemotherapy is allowed (completed since ≥ 6 months if containing gemcitabine or platinum salts);
2. previous irradiation (external radiotherapy, brachytherapy, chemoembolization) and PDT are allowed, provided that there is at least one unidimensionally measurable target lesion in untreated area
Resolution of all side effects of prior surgical procedures to grade ≤ 1 (except for the laboratory values specified below)
At least 4 weeks from any major surgery (at first dose of study drug)
ECOG Performance Status of 0-2

Exclusion Criteria:

Surgery (except diagnostic biopsy), external radiotherapy, brachytherapy, or PDT within 30 days prior to start of treatment.
Other tumor type than adenocarcinoma (e.g. leiomyosarcoma, lymphoma) or a second cancer except in patients with squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix which has been effectively treated. Patients curatively treated and disease free for at least 5 years will be discussed with the sponsor before inclusion
History of cardiac disease: congestive heart failure > NYHA class 2; active CAD (MI more than 6 months prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
Any of the following within the 12 months prior to starting the study treatment,: coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack, or pulmonary embolism
Ongoing cardiac dysrhythmias of grade ≥ 2, atrial fibrillation of any grade, or QTc interval > 450 msec for males or > 470 msec for females
Hypertension that cannot be controlled by medications ( > 150/100 mmHg despite optimal medical therapy)
History of HIV infection
Active clinically serious infections ( > grade 2 NCI-CTC version 3.0)
Known Central Nervous System tumors including metastatic brain disease
Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
History of organ allograft
Patients with evidence or history of bleeding diathesis
Active disseminated intravascular coagulation, or patients prone to thromboembolism
Patients undergoing renal dialysis
Pregnant or breast-feeding patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00661830

Contacts

Contact: Markus Moehler, MD

49-613-117-5712

moehler@mail.uni-mainz.de

Locations

Germany
Klinikum der Johann-Wolfgang Goethe-Universität, Innere Medizin I, Theodor-Stern-Kai 7	Recruiting
D-60590 Frankfurt, Germany
Contact: Stefan Zeuzem, Prof., MD 0049 69 6301 ext 5122 Zeuzem@am.uni-frankfurt.de
Sub-Investigator: Jörg Trojan, MD
Principal Investigator: Stefan Zeuzem, Prof. MD
Klinikum Fulda gAG, Tumorklinik, Pacelliallee 4	Recruiting
D-36043 Fulda, Germany
Contact: Heinz-Gert Höffkes, Prof., MD 0049 661 84 ext 5487 Stefan.Gebhard@klinikum-fulda.de
Sub-Investigator: Andrea Distelrath, MD
Sub-Investigator: Stefan Gebhard
Principal Investigator: Heinz-Gert Höffkes, Prof. MD
Universitätsklinikum Hamburg-Eppendorf, I. Med. Klinik, Zentrum für Innere Medizin, Martinistr. 3	Recruiting
D-20248 Hamburg, Germany
Contact: Ansgar W. Lohse, Prof., MD 0049 40 42803 ext 3910 e.hennes@uke.uni-hamburg.de
Sub-Investigator: Ulrike Denzer, MD
Sub-Investigator: Gunter Schuch, MD
Sub-Investigator: Karin Oechsle, MD
Sub-Investigator: Elke Hennes, MD
Sub-Investigator: Stephanie Schulze, MD
Principal Investigator: Ansgar W. Lohse, Prof. MD
Klinikum der Universität München, Medizinische Klinik II, Marchioninistr. 15	Recruiting
D-81377 München, Germany
Contact: Frank T. Kolligs, PD, MD 0049 89 7095 ext 5272 Frank.kolligs@med.uni-muenchen.de
Sub-Investigator: Jutta Berster, MD
Sub-Investigator: Mark op den Winkel
Principal Investigator: Frank T. Kolligs, PD MD
Klinikum rechts der Isar, TU München, II. Medizinische Klinik und Poliklinik, Ismaningerstr. 22	Recruiting
D-81675 München, Germany
Contact: Matthias Ebert, Prof. MD 0049 89 4140 ext 6706 Studiensekretariat.med2@lrz.tum.de
Sub-Investigator: Martina Mayr, MD
Sub-Investigator: Günter Schneider, MD
Principal Investigator: Matthias Ebert, Prof. MD
II. Med. Klinik, Leopoldina-Krankenhaus der Stadt Schweinfurt, Gustav-Adolf-Str. 8	Recruiting
D-97422 Schweinfurt, Germany
Contact: Stephan Kanzler, PD MD 0049 9721 720 ext 2482 skanzler@leopoldina.de
Sub-Investigator: Hans H Reinel, MD
Principal Investigator: Stephan Kanzler, PD MD
Universitätsklinikum Marburg und Giessen GmbH, Standort Marburg, Klinik für Gastroenterologie, Baldingerstraße	Not yet recruiting
D-35043 Marburg, Germany
Contact: Thomas Gress, Prof. MD 0049 6421 286 ext 6460 michlp@med.uni-marburg.de
Sub-Investigator: Patrick Michl, PD MD
Sub-Investigator: Heiko Fensterer, MD
Sub-Investigator: Daniela Müller, MD
Principal Investigator: Thomas Gress, Prof. MD
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II, Kirrberger Str., Gebäude 41	Recruiting
D-66421 Homburg/Saar, Germany
Contact: Jochen Rädle, PD MD 0049 6841 16 ext 23223 injrae@uniklikum-saarland.de
Sub-Investigator: Bernhard Jüngling, MD
Sub-Investigator: Simone Weidner, MD
Principal Investigator: Jochen Rädle, PD MD
Vivantes Klinikum Am Urban, Gastroenterologie, Dieffenbachstr. 1	Not yet recruiting
D-10967 Berlin, Germany
Contact: Hans Scherübl, Prof. MD 0049 30 130225 ext 201 hans.scheruebl@vivantes.de
Sub-Investigator: Ranja Hübner, MD
Sub-Investigator: Jan Eick, MD
Principal Investigator: Hans Scherübl, Prof. MD
Universitätsklinikum Jena, Klinik für Innere Medizin, Innere Medizin II	Recruiting
D-07740 Jena, Germany
Contact: Udo Lindig, MD 0049 3641 9324 ext 201 UKJ-KIM2@med.uni-jena.de
Sub-Investigator: Alexander Kademann, MD
Sub-Investigator: Izabella Zambrzycka, MD
Sub-Investigator: Ulrich Wedding, MD
Principal Investigator: Udo Lindig, MD
Germany, Rheinland-Pfalz
Klinikum der Johannes Gutenberg-Universität Mainz, I. Med. Klinik	Recruiting
Mainz, Rheinland-Pfalz, Germany, 55131
Contact: Markus Moehler, MD 0049 6131 175712 moehler@mail.uni-mainz.de
Principal Investigator: Markus Moehler, MD
Sub-Investigator: Martin Götz, MD
Sub-Investigator: Lyros Orestis, MD
Sub-Investigator: Jürgen Siebler, MD
Sub-Investigator: Marcus Wörns, MD
Sub-Investigator: Martin Sprinzl, MD

Sponsors and Collaborators

Johannes Gutenberg University Mainz

Johannes Gutenberg University Mainz, interdisciplinary Center Clinical Trials

Investigators

Principal Investigator:

Markus Moehler, MD

Johannes Gutenberg University Mainz, I. Med. Klinik

More Information

Responsible Party:	Johannes Gutenberg University Mainz, I. Med. ( PD Dr. med. Markus Moehler )
Study ID Numbers:	CC-GEMSO-2007
Study First Received:	April 15, 2008
Last Updated:	September 5, 2008
ClinicalTrials.gov Identifier:	NCT00661830
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Johannes Gutenberg University Mainz:

advanced
metastatic
biliary
tract

Study placed in the following topic categories:

Biliary tract cancer
Gemcitabine
Adenocarcinoma

Sorafenib
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs

Enzyme Inhibitors
Protein Kinase Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 15, 2009