Riluzole and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase I Trial of Riluzole in Combination With Radiation Therapy in Patients Undergoing Whole Brain Radiation Therapy for Brain Metastasis

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01018836
• Other study ID #: 050808
• Secondary ID: CDR0000660044P30
• Status: Terminated
• Phase: Phase 1
• First received: November 24, 2009
• Last updated: April 30, 2014
• Start date: November 2009
• Est. completion date: December 2013

Study information

• Verified date: April 2014
• Source: Rutgers, The State University of New Jersey
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• riluzole
The first dose of Riluzole will be day 0 of study enrollment. WBRT must begin within 48 hours of the initiation of Riluzole therapy. At the completion of radiation, Riluzole should be discontinued and steroids should be tapered over the course of 1-3 weeks, at the discretion of the treating physicians.

Radiation:
• whole-brain radiation therapy
Standard whole brain irradiation will be carried out at 250 cGy per day fractions times 15 to a total dose of 3750 cGy using a standard opposed lateral helmet field with the inferior border inclusive of C1.

Locations

Country	Name	City	State
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
Rutgers, The State University of New Jersey	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of riluzole		2.5 years	Yes
Secondary	Long-term toxicity of riluzole		.25 years	Yes
Secondary	Neurocognitive function before and after treatment		2.5 years	No
Secondary	MRI response of brain metastasis after treatment		2.5 years	No
Secondary	Survival		2.5 years	No
Secondary	Response of brain metastasis to treatment as a function of the expression of glutamate receptors		2.5 years	No