Riluzole in Treating Patients With Stage III or Stage IV Melanoma That Can Be Removed by Surgery

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Riluzole may stop or slow the growth of tumor cells and may be an effective treatment for melanoma. PURPOSE: This early phase I trial is studying how well riluzole works in treating patients with stage III or stage IV melanoma that can be removed by surgery.

Detailed Description
-----------------
OBJECTIVES: Primary To evaluate the potential effects of glutamate receptor blockade on cellular pathways important in the genesis and progression of melanoma in patients with stage III or IV melanoma undergoing surgical resection. To determine whether treatment with riluzole alters expression of activated PLC and ERK in lysates from tumor tissue biopsies. Secondary Determine if treatment with riluzole affects the overall metabolic activity of melanoma tumors as measured by pre- and post-treatment PET scanning, pre- and post-treatment tumor mitotic rate evaluation, and pre- and post-treatment immunohistochemical staining for Ki-67. OUTLINE: Patients receive oral riluzole twice daily for 14 days. Within 24 hours after the final dose of riluzole, patients undergo standard surgical resection. Patients undergo tumor tissue sample collection at baseline and during surgery for laboratory studies. Samples are analyzed by routine histology, immunohistochemistry, western blotting, and RT-PCR for Grm1 expression, - RAS and B-raf mutations, PLC and MAP kinase activity, Ki-67 staining, and mitotic rate. Patients also undergo blood sample collection periodically for pharmacokinetics studies. PET scans are obtained before and after treatment to evaluate the overall metabolic activity of the tumor and how this activity changes with inhibition of the Grm1 pathway.

Official Title
-----------------
A Phase 0 Trial of Riluzole in Patients With Resectable Stage III and IV Melanoma

Conditions
-----------------
Melanoma (Skin)

Intervention / Treatment
-----------------
* Drug: riluzole
* Genetic: protein expression analysis
* Genetic: reverse transcriptase-polymerase chain reaction
* Genetic: western blotting
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Other: pharmacological study
* Procedure: neoadjuvant therapy
* Procedure: therapeutic conventional surgery


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed melanoma Stage III or IV disease Must have at least two resectable tumors or a tumor large enough to undergo pre-treatment core needle biopsy Must be eligible for resection of disease with curative or palliative intent PATIENT CHARACTERISTICS: ECOG performance status 0 or 1 ANC ≥ 1,000/mm³ Platelet count ≥ 50,000/mm³ AST/ALT ≤ 3 times upper limit of normal (ULN) Total bilirubin normal Calculated creatinine clearance ≥ 50 mL/min INR ≤ 25% of ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 48 hours after completion of study treatment No history of allergic reaction to riluzole or similar compounds No known history of hepatitis B or C PRIOR CONCURRENT THERAPY: Not specified

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: riluzole|nan|
|Genetic: protein expression analysis|nan|
|Genetic: reverse transcriptase-polymerase chain reaction|nan|
|Genetic: western blotting|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|
|Other: pharmacological study|nan|
|Procedure: neoadjuvant therapy|nan|
|Procedure: therapeutic conventional surgery|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the inhibition of components of the Grm1 signaling cascade |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mitoses in nodal metastases and Ki-67 immunostaining (0-3+ scale) |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage III melanoma, stage IV melanoma