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

University of Medicine and Dentistry of New Jersey

Status and phase: Terminated; Phase 1

Conditions: Melanoma (Skin)

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

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00667901

P30CA072720 (U.S. NIH Grant/Contract)

CDR0000592958

CINJ-IRB-0220060225

CINJ-090603

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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