This phase I trial studies the side effects and best dose of sorafenib tosylate when given together with riluzole in treating patients with solid tumors or melanoma that has spread to other places in the body and usually cannot be cured or controlled with treatment. Riluzole may stop or slow the growth of tumor cells. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving riluzole together with sorafenib tosylate may kill more tumor cells.
PRIMARY OBJECTIVES: I. To define a safe dose of sorafenib (sorafenib tosylate) to combine with riluzole in the treatment of patients with all types of solid tumors refractory to standard therapy or for whom no standard therapy exists. SECONDARY OBJECTIVES: I. To examine the correlation of clinical or radiologic response with signaling through the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways. II. To determine if response to therapy with riluzole and sorafenib correlates with expression levels of B-cell lymphoma (BCL)-2, myeloid cell leukemia (MCL)-1, or BCL2-like 11 (apoptosis facilitator) (BIM). III. To characterize the pharmacokinetics of the combination of riluzole with sorafenib and determine if any drug-drug interactions exist. IV. To evaluate the microvesicle (an inter-cellular communication approach which may cargo proteins, ribonucleic acids \[RNAs\] and deoxyribonucleic acids \[DNAs\] to its host cell) quantification difference between pre-treatment and post-treatment peripheral blood samples of patients. OUTLINE: This is a dose-escalation study of sorafenib tosylate. Patients receive riluzole orally (PO) twice daily (BID) and sorafenib tosylate PO once daily (QD) or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up for approximately 2-3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Maximum-tolerated dose of sorafenib tosylate and riluzole in patients with all types of solid tumors
Maximum tolerated dose is defined as the first dose level at which exactly 2/6 patients experience dose limiting toxicity, or at which 1/6 experience dose limiting toxicity and (due to de-escalation) at least 2/3 or 3/6 patients treated with the next higher dose level had dose limiting toxicity.
Time frame: 28 days
Suppression of MAPK and PI3K/AKT pathways
Will examine the correlation of clinical or radiologic response with signaling.
Time frame: Up to 3 years
Change in BCL-2 expression
Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.
Time frame: Baseline to 3 years
Change in MCL-1 expression
Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.
Time frame: Baseline to 3 years
Change in BIM expression
Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.
Time frame: Baseline to 3 years
Pharmacokinetic parameters of the combination of riluzole with sorafenib tosylate
Will be assessed from blood samples.
Time frame: On days 2, 8, 10, and 15 of each course
Change in microvesicle quantification
Will be assessed from blood samples.
Time frame: Baseline to 3 years
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