Efficacy and Safety of Sunitinib in Metastatic Gastric Cancer
This trial will be conducted to evaluate the efficacy, safety, and tolerability of sunitinib (sunitinib-malate) as a second-line palliative therapy in metastatic gastric cancer. Despite the efforts in front-line therapy, second-line protocols have not yet been established in randomized clinical trials for those patients. Although many patients are still in good performance status and present with low tumor burden after failure of first-line chemotherapy, they may clearly benefit from second-line treatment. Increasingly more metachronic metastatic patients are urging for new platinum-free therapeutic options due to the fast-growing use of (neo-) adjuvant platin-based protocols.
So far, only sparse data on chemotherapy are available after failure of platin-based protocols. Nearly only irinotecan-containing combinations have properly been analyzed, and produced excellent response rates and survival times of up to 30% and 7.6 months, respectively. However, irinotecan has not been approved yet for this indication. In addition, as irinotecan-containing regimens have been submitted for approval for first-line therapy, second-line regimens in irinotecan-refractory patients have not been evaluated in any trial. Thus, there is an urgent need to establish new second-line treatment options for both, cisplatinum- or irinotecan-combination refractory patients with advanced or metastatic gastric cancer.
Sunitinib inhibits the receptor tyrosine kinases (RTKs) involved in tumor proliferation and angiogenesis, specifically the VEGFR, PDGFR, KIT, FLT-3, and RET. The VEGF pathway has been shown to be a significant factor in metastatic gastric cancer. In gastric carcinoma cells, VEGF ligands and its receptors are definitely involved in the process of tumor progression. KDR and FLT-1 are expressed widely and VEGF stimulated KDR-positive tumor cell growth directly. The ligand VEGF-C has also been shown to be involved in progression of human gastric carcinoma, particularly via lymphangiogenesis. In addition, peritoneal metastases of some cancers such as gastric cancers were largely dependent on VEGF. Therefore, patients with chemo-refractory metastatic gastric cancer might benefit from VEGFR inhibitory therapy with sunitinib.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-label, Multicenter Phase II Trial of Sunitinib for Patients With Chemo-refractory Metastatic Gastric Cancer|
- Objective Response Rate (ORR) [ Time Frame: one year ] [ Designated as safety issue: No ]The primary endpoint is the ORR within the first 6 treatment cycles, defined as the percentage of participants with a confirmed reduction in tumor size fulfilling the criteria for complete or partial response (CR or PR) according to RECIST. CR=disappearance of all target lesions, PR=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions
- Progression-Free Survival (PFS) [ Time Frame: one year ] [ Designated as safety issue: No ]PFS is defined as the time from first dose of trial medication to first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
- Overall Survival (OS) [ Time Frame: one year ] [ Designated as safety issue: No ]OS is defined as the time from the first dose of trial medication to date of death due to any cause.
- One-Year Survival [ Time Frame: one year ] [ Designated as safety issue: Yes ]One-year survival is defined as the percentage of participants surviving for at least one year after first dose of trial medication.
- Adverse Events [ Time Frame: one year ] [ Designated as safety issue: Yes ]The number of participants with at least one adverse event was measured.
- Safety and Tolerability: Serious Adverse Events [ Time Frame: one year ] [ Designated as safety issue: Yes ]The number of participants with at least one Serious Adverse Event was measured.
- Safety and Tolerability: Adverse Events in ≥10% of Patients [ Time Frame: one year ] [ Designated as safety issue: Yes ]
|Study Start Date:||December 2006|
|Study Completion Date:||August 2009|
|Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
|Universität Heidelberg, Nationales Zentrum für Tumorerkrankungen|
|Heidelberg, Baden-Würtemberg, Germany, 69120|
|Tübingen, Baden-Würtemberg, Germany, 72076|
|TU München, Klinikum rechts der Isar, II. Med. Klinik und Poliklinik|
|München, Bayern, Germany, 81675|
|Klinikum der Universität Würzburg|
|Würzburg, Bayern, Germany, 97070|
|Universitätsklinikum der GHS Essen, Innere Klinik und Poliklinik, Tumorforschung|
|Essen, Nordrhein-Westfalen, Germany, 45122|
|Universitätsklinik zu Köln, Klinik I für Innere Medizin|
|Köln, Nordrhein-Westfalen, Germany, 50937|
|Klinikum der Johannes Gutenberg-Universität Mainz|
|Mainz, Rheinland-Pfalz, Germany, 55131|
|Universitätsklinikum des Saarlandes|
|Homburg/Saar, Saarland, Germany, 66421|
|Magdeburg, Sachsen-Anhalt, Germany, 39120|
|Universitätsklinikum Carl Gustav Carus, Med. Klinik I|
|Dresden, Sachsen, Germany, 01307|
|Charité, Campus Benjamin Franklin|
|Berlin, Germany, 12200|
|KH Nordwest, Abteilung für Hämatologie und Onkologie|
|Frankfurt, Germany, 60488|
|Principal Investigator:||Markus Moehler, MD||Johannes-Gutenberg-University of Mainz, I. Dept. Internal Medicine|