Melanoma (Skin)
Conditions
Keywords
stage III melanoma, stage IV melanoma
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.
Interventions
DRUGriluzole
GENETICprotein expression analysis
GENETICreverse transcriptase-polymerase chain reaction
GENETICwestern blotting
OTHERimmunohistochemistry staining method
OTHERlaboratory biomarker analysis
OTHERpharmacological study
PROCEDUREneoadjuvant therapy
PROCEDUREtherapeutic conventional surgery
Sponsors
National Cancer Institute (NCI)
University of Medicine and Dentistry of New Jersey
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measurement of the inhibition of components of the Grm1 signaling cascade | — |
Secondary
| Measure | Time frame |
|---|---|
| Mitoses in nodal metastases and Ki-67 immunostaining (0-3+ scale) | — |
Countries
United States
Outcome results
None listed