Efficacy and Safety of Sunitinib in Metastatic Gastric Cancer

Gastric Adenocarcinoma Clinical Trial

Official title: An Open-label, Multicenter Phase II Trial of Sunitinib for Patients With Chemo-refractory Metastatic Gastric Cancer

Status Completed

Clinical Trial Summary

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.

Clinical Trial Description

n/a

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Barrett Esophagus
• Gastric Adenocarcinoma

• NCT number: NCT00411151
• Study type: Interventional
• Source: Johannes Gutenberg University Mainz
• Status: Completed
• Phase: Phase 2
• Start date: December 2006
• Completion date: August 2009