RATIONALE: Everolimus may stop the growth of stomach or esophageal cancer by blocking blood flow to the tumor. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing, or by stopping them from spreading. Giving everolimus together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with combination chemotherapy in treating patients with metastatic stomach or esophageal cancer that has spread to other places in the body.
OBJECTIVES: I. To determine the maximum tolerated dose of everolimus to use in combination with mFOLFOX6 \[oxaliplatin, leucovorin (leucovorin calcium), 5-FU (fluorouracil)\]. II. To better describe the toxicities associated with the combination of everolimus with mFOLFOX6. III. To assess response rate and progression-free survival in this patient population. IV. To assess overall survival in patients with metastatic gastric, esophageal and gastroesophageal junction (GEJ) adenocarcinoma treated with the combination of mFOLFOX6 + everolimus. OUTLINE: This is a dose-escalation study of everolimus. Patients receive fluorouracil intravenously (IV) continuously over 46 hours, leucovorin calcium IV over 2 hours, and oxaliplatin IV over 2 hours on day 1. Patients also receive oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically for 1 year.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Given IV
Given IV
Given IV
Given orally
Correlative studies
Correlative studies
Correlative studies
City of Hope Medical Center
Duarte, California, United States
South Pasadena Cancer Center
South Pasadena, California, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Maximum Tolerated Dose (MTD) of Everolimus
The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. Toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: Course 1 (first 28 days)
Number of Subject With Overall Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 5 years
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. From the date treatment started until the date of first documented progression or date of death from any cause, whichever came first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: up to 5 years
Overall Survival
Estimated using the product-limit method of Kaplan and Meier. From the date treatment started until the date of death from any cause.
Time frame: Up to 5 years.
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