Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma
|Advanced Malignant Solid Neoplasm Recurrent Melanoma Refractory Malignant Solid Neoplasm Stage III Skin Melanoma Stage IIIA Skin Melanoma Stage IIIB Skin Melanoma Stage IIIC Skin Melanoma Stage IV Skin Melanoma||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Riluzole Drug: Sorafenib Tosylate||Phase 1|
|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, 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.
- 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 ]Will be assessed from blood samples.
- Pharmacokinetic parameters of the combination of riluzole with sorafenib tosylate [ Time Frame: On days 2, 8, 10, and 15 of each course ]Will be assessed from blood samples.
- Suppression of MAPK and PI3K/AKT pathways [ Time Frame: Up to 3 years ]Will examine the correlation of clinical or radiologic response with signaling.
|Actual Study Start Date:||February 18, 2011|
|Estimated Primary Completion Date:||September 1, 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|
|New Brunswick, New Jersey, United States, 08903|
|Principal Investigator:||Janice Mehnert||Rutgers Cancer Institute of New Jersey|