Clinical trial NCT01018836: Riluzole and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases
Official title: A Phase I Trial of Riluzole in Combination With Radiation Therapy in Patients Undergoing Whole Brain Radiation Therapy for Brain Metastasis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Metastatic Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: tumors metastatic to brain
unspecified adult solid tumor, protocol specific
Lead sponsor: Rutgers, The State University of New Jersey
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-11-25
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs, such as riluzole, may make tumor cells more sensitive to radiation therapy. Giving riluzole together with whole-brain radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of riluzole when given together with whole-brain radiation therapy in treating patients with brain metastases.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum tolerated dose of riluzole that can be administered concurrently with standard whole-brain radiotherapy (WBRT) in patients with multiple brain metastases.

Secondary

* To determine the long-term toxicity of riluzole when administered with WBRT.
* To assess neurocognitive function before and after treatment with riluzole and WBRT.
* To determine the MRI response of brain metastasis after treatment with riluzole and WBRT.
* To compare survival of patients treated with riluzole and WBRT to published historical data for patients with brain metastases.
* To evaluate the response of brain metastasis to riluzole and WBRT as a function of the expression of glutamate receptors on the primary tumor specimen.

OUTLINE: This is a dose-escalation study of riluzole.

Patients receive oral riluzole twice daily beginning on day 0. Beginning within 2 days after the initiation of riluzole, patients undergo whole-brain radiotherapy for 15 fractions.

Patients undergo neurocognitive and quality-of-life assessments at baseline, at 5 weeks, and at 3 months.

Tumor tissue samples are collected for laboratory biomarker studies.

After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed solid tumor
* Has ≥ 2 brain metastases as demonstrated by baseline MRI

  * Patients with only 1 metastasis are eligible provided the metastasis is too large for radiosurgery and not amenable to surgical resection
* Not being considered for surgical resection
* Eligible to undergo whole-brain radiotherapy (WBRT)

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* ANC ≥ 1,000/μL
* Platelet count ≥ 50,000/μL
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST/ALT ≤ 1.5 times ULN
* INR ≤ 1.5 times ULN
* Sodium normal
* Thyroid-stimulating hormone normal
* Negative pregnancy test
* Fertile patients must use effective contraception before, during, and for ≥ 6 months after completion of study treatment
* No headaches, disequilibrium, vertigo, or dizziness
* No known history of hepatitis B or C
* No concurrent serious systemic disorder (including active infection) 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

PRIOR CONCURRENT THERAPY:

* No prior WBRT
* At least 2 weeks since prior systemic chemotherapy
* No systemic chemotherapy during and for ≥ 3 weeks after completion of WBRT
* Radiosurgical boosts to ≤ 3 metastases allowed, based on the discretion of the treating radiation oncologist

Primary outcomes:
measure: Maximum tolerated dose of riluzole
timeFrame: 2.5 years
Secondary outcomes:
measure: Long-term toxicity of riluzole
timeFrame: .25 years
measure: Neurocognitive function before and after treatment
timeFrame: 2.5 years
measure: MRI response of brain metastasis after treatment
timeFrame: 2.5 years
measure: Survival
timeFrame: 2.5 years
measure: Response of brain metastasis to treatment as a function of the expression of glutamate receptors
timeFrame: 2.5 years
Other outcomes:
Locations:
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
Study officials:
affiliation: Rutgers Cancer Institute of New Jersey
name: Bruce G. Haffty, MD
role: PRINCIPAL_INVESTIGATOR
References: