Gemcitabine and Sorafenib in Advanced Biliary Tract Cancer (GEMSO)
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|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|
- Progression-free Survival (PFS) [ Time Frame: one year ] [ Designated as safety issue: No ]The primary endpoint is the progression-free survival (PFS) defined as the time from start of treatment to first documentation of objective tumor progression or to death due to any cause, whichever occurs first during treatment or follow-up period. For patients not known to have died as of the data cut-off date and who do not have objective progressive disease, PFS will be censored at the date of the last objective progression-free disease assessment. For patients who receive subsequent anticancer therapy (after discontinuation from the study drug) prior to objectively determined disease progression or death, PFS will be censored at the date of the last objective progression-free disease assessment prior to post-discontinuation anti-cancer therapy. Acceptable documentation of objective disease progression status consists of objective assessments using CT scan assessment method.
- Overall Survival [ Time Frame: one year ] [ Designated as safety issue: Yes ]Overall Survival (OS) is measured from start of treatment to death due to any cause until end of follow-up period. Time to last observation will be used if a patient has not died and OS for the patient will be considered censored at the date of the last observation.
- Best Overall Response [ Time Frame: one year ] [ Designated as safety issue: No ]
Best Overall Response (BOR) is defined as the best tumor response (confirmed partial or complete response, stable disease) that is achieved during treatment or within 30 days after termination of active therapy that is confirmed according to the RECIST tumor response criteria. Best response is determined from the sequence of responses assessed. For complete response (CR) or partial response (PR), best response must be confirmed by a second assessment within 4 -6 weeks.
Two objective status determinations of CR before progression are required for a best response of CR.
Two determinations of PR or better before progression, but not qualifying for a CR, are required for a best response of PR.
Best response of Stable Disease (SD) is defined as disease that does not meet the criteria of CR, PR or Progressive Disease (PD) and has been evaluated at least one time, at least 6 weeks after baseline assessment.
- Time to Objective Response [ Time Frame: one year ] [ Designated as safety issue: No ]Time to Objective Response (OR) is defined as the time from start of treatment to objective tumor response (CR or PR) is first documented according to the RECIST tumor response criteria during treatment or until 30 days after termination of active therapy. Response must subsequently be confirmed. For subjects failing to achieve an objective response and who did not progress during the trial, time to objective response will be censored at their last date of tumor evaluation.
|Study Start Date:||May 2008|
|Study Completion Date:||June 2010|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
Gemcitabine + Sorafenib
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.Drug: Sorafenib
Sorafenib 400 mg bid orally continuously
Placebo Comparator: 2
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.Drug: Placebo
|Klinikum der Johannes Gutenberg-Universität Mainz, I. Med. Klinik|
|Mainz, Rheinland-Pfalz, Germany, 55131|
|Universitätsklinikum Jena, Klinik für Innere Medizin, Innere Medizin II|
|D-07740 Jena, Germany|
|Universitätsklinikum Hamburg-Eppendorf, I. Med. Klinik, Zentrum für Innere Medizin, Martinistr. 3|
|D-20248 Hamburg, Germany|
|Klinikum Fulda gAG, Tumorklinik, Pacelliallee 4|
|D-36043 Fulda, Germany|
|Klinikum der Johann-Wolfgang Goethe-Universität, Innere Medizin I, Theodor-Stern-Kai 7|
|D-60590 Frankfurt, Germany|
|Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II, Kirrberger Str., Gebäude 41|
|D-66421 Homburg/Saar, Germany|
|Klinikum der Universität München, Medizinische Klinik II, Marchioninistr. 15|
|D-81377 München, Germany|
|Klinikum rechts der Isar, TU München, II. Medizinische Klinik und Poliklinik, Ismaningerstr. 22|
|D-81675 München, Germany|
|II. Med. Klinik, Leopoldina-Krankenhaus der Stadt Schweinfurt, Gustav-Adolf-Str. 8|
|D-97422 Schweinfurt, Germany|
|Esslingen, Germany, 73730|
|Universitätsklinikum Halle, Innere Medizin I|
|Halle, Germany, 06120|
|Principal Investigator:||Markus Moehler, MD||Johannes Gutenberg University Mainz, I. Med. Klinik|