Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma
|ClinicalTrials.gov Identifier: NCT01303341|
Recruitment Status : Active, not recruiting
First Posted : February 24, 2011
Last Update Posted : May 16, 2018
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Solid Neoplasm Recurrent Melanoma Refractory Malignant Solid Neoplasm Stage III Cutaneous Melanoma AJCC v7 Stage IIIA Cutaneous Melanoma AJCC v7 Stage IIIB Cutaneous Melanoma AJCC v7 Stage IIIC Cutaneous Melanoma AJCC v7 Stage IV Cutaneous Melanoma AJCC v6 and v7||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Riluzole Drug: Sorafenib Tosylate||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Riluzole and Sorafenib in Patients With Advanced Solid Tumors and Melanoma|
|Actual Study Start Date :||February 18, 2011|
|Estimated Primary Completion Date :||December 1, 2018|
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
Other: Pharmacological Study
Other Name: Rilutek
Drug: Sorafenib Tosylate
- 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.
- Suppression of MAPK and PI3K/AKT pathways [ Time Frame: Up to 3 years ]Will examine the correlation of clinical or radiologic response with signaling.
- 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 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 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.
- 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.
- Change in microvesicle quantification [ Time Frame: Baseline to 3 years ]Will be assessed from blood samples.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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|