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A Phase I Trial of Riluzole and Sorafenib in Patients With Advanced Solid Tumors and Melanoma

Phase 1
18 Years
Open (Enrolling)
Recurrent Melanoma, Stage IIIA Melanoma, Stage IIIB Melanoma, Stage IIIC Melanoma, Stage IV Melanoma, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Trial of Riluzole and Sorafenib in Patients With Advanced Solid Tumors and Melanoma


I. To define a safe dose of 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
MAPK and PI3K/AKT pathways.

II. To determine whether response to therapy with riluzole and sorafenib tosylate correlates
with expression levels of BCL-2, MCL-1, or BIM.

III. To characterize the pharmacokinetics of the combination of riluzole with sorafenib
tosylate and determine if any drug-drug interactions exist.

IV. To evaluate the microvesicle (an inter-cellular communication approach which may cargo
proteins, RNAs and 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 followed by an
expansion-cohort study.

Patients receive riluzole orally (PO) twice daily and sorafenib tosylate PO once daily on
days 1-28. Courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

Blood samples are collected at baseline and periodically during course 1 for pharmacokinetic
studies. Some patients undergo tumor biopsies at baseline and prior to course 2 for
correlative studies.

After completion of study therapy, patients are followed up for approximately 2-3 years.

Inclusion Criteria:

- Patients must have histologically proven solid tumors refractory to standard therapy
or for whom no standard therapy exists (Phase I), OR stage III unresectable melanoma
or stage IV metastatic melanoma with tumor amenable to biopsy (expansion cohort)

- Measurable or evaluable disease

- Patients with brain lesions that have been treated and clinically stable for at least
4 weeks, and who are not taking steroids and/or enzyme-inducing anticonvulsants, are

- ECOG performance status 0-2

- ANC ≥ 1,500/μL

- Platelet count ≥ 100,000/μL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN

- INR ≤ 1.5 times ULN

- Creatinine ≤ 2 times ULN

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal, barrier method of birth control, or abstinence) prior to study entry, for
the duration of study participation, and for 2 weeks after discontinuation of
riluzole and/or sorafenib tosylate

- Not pregnant or nursing

- Negative pregnancy test

- No serious concomitant systemic disorders (including active infections) that would
compromise the safety of the patient or compromise the patient's ability to complete
the study, at the discretion of the investigator

- No history of allergic reactions attributed to riluzole or sorafenib tosylate

- No known human immunodeficiency virus (HIV) infection, or known history of active
hepatitis B or C infection

- No cardiac disease, including NYHA > class II congestive heart failure, unstable
angina (anginal symptoms at rest), or new-onset angina (began within the last 3

- No history of stroke within the past six months

- No clinically significant peripheral vascular disease

- No cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

- No uncontrolled hypertension, defined as systolic blood pressure > 150 mm Hg or
diastolic blood pressure > 90 mm Hg, despite optimal medical management

- No active clinically serious infection > CTCAE grade 2

- None of the following within 6 months prior to first-dose of treatment: myocardial
infarction, symptomatic coronary artery disease (severe or unstable angina), artery
bypass graft, uncontrolled arrhythmias, symptomatic congestive heart failure,
cerebrovascular accident or transient ischemic attack, or pulmonary embolus

- No pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 or any other
hemorrhage/bleeding event ≥ CTCAE grade 3 within 4 weeks of first-dose of study drug

- No evidence or history of bleeding diathesis or coagulopathy

- No condition that would impair the patient's ability to swallow whole pills

- No malabsorption problem

- No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 1 of treatment

- No serious, non-healing wound, ulcer, or bone fracture

- No significant traumatic injury within the first 4 weeks of study therapy

- Able to comply with study and/or follow-up procedures

- No concurrent grapefruit or grapefruit juice

- Prior unlimited therapies are permitted for patients enrolled in the dose-escalation
phase of the study

- Patients in the expansion cohort of the study may not have any prior therapy
with riluzole or sorafenib tosylate

- More than 4 weeks since prior chemotherapy, radiotherapy, or biologic agents (6 weeks
for nitrosoureas or mitomycin C) and recovered from adverse events

- At least 4 weeks since any prior major surgery and no anticipation of need for major
surgical procedure during the course of the study

- Concurrent hormonal therapy for patients with prostate cancer allowed

- Concurrent anticoagulation with Lovenox (enoxaparin) is permitted, however, patients
on anticoagulation with warfarin are not permitted on this study

- No concurrent, recent (within 4 weeks of the first treatment of this study), or
planned participation in another experimental drug study

- Concurrent prevention trials are permitted if the trial is not testing a novel
experimental agent

- No concurrent drugs that are substrates of CYP2B or CYP2C8, or inducers of CYP3A4

- No concurrent strong inhibitors or inducers of the isoenzyme CYP1A2

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose of sorafenib tosylate and riluzole in patients with all types of solid tumors

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Janice Mehnert

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer Institute of New Jersey


United States: Food and Drug Administration

Study ID:




Start Date:

February 2011

Completion Date:

Related Keywords:

  • Recurrent Melanoma
  • Stage IIIA Melanoma
  • Stage IIIB Melanoma
  • Stage IIIC Melanoma
  • Stage IV Melanoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • Melanoma
  • Neoplasms



Cancer Institute of New Jersey New Brunswick, New Jersey  08901