Clinical trial NCT00515216
Conditions: Stomach Neoplasms Esophageal Neoplasms
Keywords: Phase II Gastric cancer Gastroesophageal cancer Metastatic FOLFOX Thymidylate synthase Pharmacogenomic
Sponsor: Vanderbilt University
Start date: 2007-08-01; Completion date: 2013-11-01
Enrollment: 26 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study is for patients who have stomach cancer or cancer of the lower part of the esophagus that has spread to other organs. There are many different chemotherapy treatments for this type of cancer. At the present time, there is no general agreement on the way to choose the most beneficial therapy for an individual patient. Patients with different genetic backgrounds may respond differently to the same chemotherapy treatments. In this study the investigators will use a certain genetic difference in an important gene (thymidylate synthase or TS gene) to see whether treating patients who have a particular type of that gene will respond better to a standard chemotherapy regimen. The investigators are hoping that by treating patients according to their genes, that they may respond to treatment of their cancer better and it will help the investigators choose cancer treatments better in the future.

Detailed description:
Gastric and gastroesophageal junction (GEJ) cancers are a leading cause of cancer mortality. Despite the development of newer chemotherapies, the response rates and median survival in patients with these tumors has remained essentially stagnant. Defining host and molecular/biologic tumor characteristics to customize treatment may lead to improved survival outcomes. Retrospective studies have identified genetic markers that predict treatment outcome. However, there have been no prospective studies in gastric and GEJ cancer evaluating the clinical utility of these genetic factors. We hypothesize that genomically based treatment will improve the expected response rate in patients with gastric and GEJ cancers. We propose a prospective, multi-institutional Phase II clinical trial testing a germline polymorphism in the thymidylate synthase (TS) gene, the number of tandem repeats in the TS enhancer region (TSER) as a treatment selection marker. The polymorphic variant conferring three tandem repeats (TSER\*3) has been associated with 5-FU resistance due to high tumor TS expression in comparison to the TSER\*2 variant (two tandem repeats). The TSER\*3 polymorphism is common (allelic frequency of 0.5-0.8). In the proposed study, we will prospectively genotype patients with gastric and GEJ cancers. Patients who are expected to be 5-FU sensitive (carrying a TSER\*2 allele) will receive a 5-FU containing regimen (5-FU, leucovorin, oxaliplatin). Patients who are expected to be 5-FU resistant (homozygous for TSER\*3) will not be included in the study. In completing this study, we will determine whether treatment selection based on germline TSER polymorphism status improves the response rate in patients with metastatic gastric and GEJ tumors. Additional correlative studies are proposed to identify confounding factors that may alter the expected outcomes of this treatment approach.

Arms: arm 1: "Good risk" patients with the TSER\*2/\*2 or \*2/\*3 genotype or low TS expression genotype received treatment of oxaliplatin, leucovorin given over 2 hours along with 5-FU given as intravenous push followed by 5-FU given as intravenous infusion of 46 hours. This treatment was repeated every 2 weeks.
Interventions: intervention 1: 5-fluorouracil intervention 2: Oxaliplatin intervention 3: Leucovorin
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents: