Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma
This phase I trial studies the side effects and best dose of sorafenib tosylate when given together with riluzole in treating patients with advanced solid tumors or melanoma. 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.
Stage IIIA Melanoma
Stage IIIB Melanoma
Stage IIIC Melanoma
Stage IV Melanoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: sorafenib tosylate
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 ] [ Designated as safety issue: Yes ]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.
- Suppression of MAPK and PI3K/AKT pathways [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
- Change in BCL-2 expression [ Time Frame: Baseline to 3 years ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.
- Pharmacokinetic parameters of the combination of riluzole with sorafenib tosylate [ Time Frame: On days 2, 8, 10, and 15 of each course ] [ Designated as safety issue: No ]
- Change in microvesicle quantification [ Time Frame: Baseline to 3 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2011|
|Estimated Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (riluzole and sorafenib tosylate)
Patients receive riluzole PO BID and sorafenib tosylate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other Name: RilutekDrug: sorafenib tosylate
Other Names:Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
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) 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 firstname.lastname@example.org|
|Principal Investigator: Janice M. Mehnert|
|Principal Investigator:||Janice Mehnert||Rutgers Cancer Institute of New Jersey|