Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma
Adult Solid Neoplasm
Stage IIIA Skin Melanoma
Stage IIIB Skin Melanoma
Stage IIIC Skin Melanoma
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Drug: Sorafenib Tosylate
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of Riluzole and Sorafenib in Patients With Advanced Solid Tumors and Melanoma|
- Maximum-tolerated dose of sorafenib tosylate and riluzole in patients with all types of solid tumors [ Time Frame: 28 days ]Maximum tolerated dose is defined as the first dose level at which exactly 2/6 patients experience dose limiting toxicity (DLT), or at which 1/6 experience DLT and (due to de-escalation) at least 2/3 or 3/6 patients treated with the next higher dose level had DLT.
- Change in BCL-2 expression [ Time Frame: Baseline to 3 years ]Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.
- Change in BIM expression [ Time Frame: Baseline to 3 years ]Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.
- Change in MCL-1 expression [ Time Frame: Baseline to 3 years ]Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.
- Change in microvesicle quantification [ Time Frame: Baseline to 3 years ]
- Pharmacokinetic parameters of the combination of riluzole with sorafenib tosylate [ Time Frame: On days 2, 8, 10, and 15 of each course ]
- Suppression of MAPK and PI3K/AKT pathways [ Time Frame: Up to 3 years ]
|Study Start Date:||February 2011|
|Estimated Primary Completion Date:||March 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (riluzole and sorafenib tosylate)
Patients receive riluzole PO BID and sorafenib tosylate PO QD or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Correlative studiesDrug: Riluzole
Other Name: RilutekDrug: Sorafenib Tosylate
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01303341
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey||Recruiting|
|New Brunswick, New Jersey, United States, 08903|
|Contact: Janice M. Mehnert 732-235-6031 email@example.com|
|Principal Investigator: Janice M. Mehnert|
|Principal Investigator:||Janice Mehnert||Rutgers Cancer Institute of New Jersey|