Clinical trial NCT00054795: Study of Neurologic Progression With Motexafin Gadolinium and Radiation Therapy (SMART)
Official title: Randomized Phase III Trial of Xcytrin® (Motexafin Gadolinium) Injection for the Treatment of Brain Metastases in Patients With Non-Small Cell Lung Cancer Undergoing Whole Brain Radiation Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain Neoplasms
Carcinoma, Non-Small-Cell Lung
Metastases, Neoplasm
Keywords: Brain Neoplasms/radiotherapy
Neoplasms/complications/prevention & control,
Neuropsychological Tests,
Metalloporphyrins/therapeutic use,
Combined Modality Therapy,
Drug therapy,
Quality of Life,
Cranial Irradiation,
Radiotherapy/Targeted,
Prospective Studies,
Neoplasm Recurrence/Local,
Treatment Outcome
Brain metastases
Brain Neoplasms/secondary
Non-small cell lung cancer
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2003-02-13
Enrollment: 550
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to determine if patients with brain metastases from non-small cell lung cancer treated with Motexafin Gadolinium and whole brain radiation therapy retain their neurologic function and ability to think for a longer time compared to patients treated with whole brain radiation therapy alone.


Eligibility criteria: Inclusion Criteria:

* Adults (≥18 years old) with radiologically proven parenchymal brain metastases from histologically confirmed non-small cell lung cancer;
* KPS score of ≥70;
* Each patient must sign a study-specific Informed Consent form

Exclusion Criteria:

* Liver metastases;
* Extracranial metastases in two or more organs;
* Known leptomeningeal metastases or subarachnoid spread of tumor;
* Prior whole brain radiation;
* Plan to use radiosurgery or radiation boost after completion of WBRT;
* Planned chemotherapy during study treatment (prior and subsequent chemotherapy is allowed);
* Prior total resection of a single brain metastasis;
* Laboratory values as follows:

LDH \> 1.3 x upper limit of normal (ULN); ANC \< 1500 /mm³; Platelets \< 50,000 /mm³; Creatinine \> 2.0 mg/dL; AST or ALT \> 2 x ULN; Total bilirubin \> 2 x ULN;

* Women who are pregnant or lactating

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Fort Smith
country: United States
state: Arkansas
city: Little Rock
country: United States
state: Arkansas
city: Berkeley
country: United States
state: California
city: Concord
country: United States
state: California
city: Greenbrae
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Montebello
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Stanford
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Hartford
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Chicago
country: United States
state: Illinois
city: Fort Wayne
country: United States
state: Indiana
city: Indianapolis
country: United States
state: Indiana
city: Shreveport
country: United States
state: Louisiana
city: Baltimore
country: United States
state: Maryland
city: Washington D.C
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Detroit
country: United States
state: Michigan
city: Grand Rapids
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: St. Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Camden
country: United States
state: New Jersey
city: Morristown
country: United States
state: New Jersey
city: Albuquerque
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Akron
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Hershey
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Knoxville
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Laredo
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Charlottesville
country: United States
state: Virginia
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Liverpool
country: Australia
state: New South Wales
city: St. Leonards
country: Australia
state: New South Wales
city: Wollongong
country: Australia
state: New South Wales
city: Herston
country: Australia
state: Queensland
city: Woollongabba
country: Australia
state: Queensland
city: East Melbourne
country: Australia
state: Victoria
city: Footscray
country: Australia
state: Victoria
city: Geelong
country: Australia
state: Victoria
city: Heidelberg
country: Australia
state: Victoria
city: Linz
country: Austria
city: Wien
country: Austria
city: Antwerpen
country: Belgium
city: Bruxelles
country: Belgium
city: Haine-Saint-Paul
country: Belgium
city: Leuven
country: Belgium
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Halifax
country: Canada
state: Nova Scotia
city: Hamilton
country: Canada
state: Ontario
city: Kingston
country: Canada
state: Ontario
city: London
country: Canada
state: Ontario
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Quebec City
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Caen
country: France
city: Lille
country: France
city: Lyon
country: France
city: Montbeliard
country: France
city: Nice
country: France
city: Pierre Benite
country: France
city: Rennes
country: France
city: Saint Herblain
country: France
city: Vandoeuvre Les Nancy
country: France
city: Villejuif
country: France
city: Aachen
country: Germany
city: Berlin
country: Germany
city: Essen
country: Germany
city: Freiberg
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Herne
country: Germany
city: Magdeburg
country: Germany
city: Munchen
country: Germany
city: Gravenhage
country: Netherlands
city: Heerlen
country: Netherlands
city: Rotterdam
country: Netherlands
Study officials:
References:
citation: Mehta MP, Shapiro WR, Glantz MJ, Patchell RA, Weitzner MA, Meyers CA, Schultz CJ, Roa WH, Leibenhaut M, Ford J, Curran W, Phan S, Smith JA, Miller RA, Renschler MF. Lead-in phase to randomized trial of motexafin gadolinium and whole-brain radiation for patients with brain metastases: centralized assessment of magnetic resonance imaging, neurocognitive, and neurologic end points. J Clin Oncol. 2002 Aug 15;20(16):3445-53. doi: 10.1200/JCO.2002.07.500.
citation: Carde P, Timmerman R, Mehta MP, Koprowski CD, Ford J, Tishler RB, Miles D, Miller RA, Renschler MF. Multicenter phase Ib/II trial of the radiation enhancer motexafin gadolinium in patients with brain metastases. J Clin Oncol. 2001 Apr 1;19(7):2074-83. doi: 10.1200/JCO.2001.19.7.2074.
citation: Rosenthal DI, Nurenberg P, Becerra CR, Frenkel EP, Carbone DP, Lum BL, Miller R, Engel J, Young S, Miles D, Renschler MF. A phase I single-dose trial of gadolinium texaphyrin (Gd-Tex), a tumor selective radiation sensitizer detectable by magnetic resonance imaging. Clin Cancer Res. 1999 Apr;5(4):739-45.
citation: Magda D, Lepp C, Gerasimchuk N, Lee I, Sessler JL, Lin A, Biaglow JE, Miller RA. Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species. Int J Radiat Oncol Biol Phys. 2001 Nov 15;51(4):1025-36. doi: 10.1016/s0360-3016(01)01810-7.
citation: Miller RA, Woodburn K, Fan Q, Renschler MF, Sessler JL, Koutcher JA. In vivo animal studies with gadolinium (III) texaphyrin as a radiation enhancer. Int J Radiat Oncol Biol Phys. 1999 Nov 1;45(4):981-9. doi: 10.1016/s0360-3016(99)00274-6.