Clinical trial NCT00121420: Study of Motexafin Gadolinium With Whole Brain Radiation Therapy Followed by Stereotactic Radiosurgery Boost in the Treatment of Patients With Brain Metastases
Official title: Phase II Trial of Motexafin Gadolinium With Whole Brain Radiation Therapy Followed by Stereotactic Radiosurgery Boost in the Treatment of Patients With Brain Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neoplasm Metastasis
Brain Neoplasms
Keywords: Brain Neoplasms/secondary
Brain neoplasms/radiotherapy
Brain metastasis
Neoplasm metastasis
Cranial irradiation
Radiosurgery
Lung Neoplasms
Breast Neoplasms
Kidney Neoplasms
Melanoma
Radiotherapy
Carcinoma, non-small cell lung
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2005-07-21
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of the study is to evaluate if motexafin gadolinium with whole brain radiation therapy followed by a stereotactic radiosurgery boost is a safe and effective treatment.

Detailed description: Patients will receive three weeks of whole brain radiation therapy concurrent with daily motexafin gadolinium during weeks 2 and 3, followed by a stereotactic radiosurgery boost concurrent with motexafin gadolinium. Patients will be followed for radiologic response, neurologic progression, and neurocognitive progression.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Karnofsky performance status (KPS) ≥ 70
* Histologically confirmed malignancy with the presence of one to four intraparenchymal brain metastases
* Each patient must sign a study-specific Informed Consent form

Exclusion Criteria:

* Previous cranial radiation
* Complete resection of all known brain metastases
* Known leptomeningeal metastases
* Known liver metastases
* Clinical or radiologic evidence of progression (other than study lesion\[s) within 1 month prior to enrollment
* Patients with metastases within 10 mm of the optic apparatus
* Patients with metastases in the brainstem, midbrain, pons, or medulla
* Planned chemotherapy during WBRT and/or SRS
* Uncontrolled hypertension
* Women who are pregnant or lactating

and 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 \> 3 x ULN
* Total bilirubin \> 2 x ULN

Primary outcomes:
measure: Rate of irreversible Grade 3 or any Grade 4 or 5 neurologic radiation toxicities occuring within 3 months following SRS boost
Secondary outcomes:
measure: Change in lesion size and number between screening MRI and SRS treatment -planning MRI
measure: Time to neuroligic progression or death with evidence of neurologic progression
measure: Time to neurocognitive progression
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Aurora
country: United States
state: Colorado
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Madison
country: United States
state: Wisconsin
city: Milwaukee
country: United States
state: Wisconsin
city: Montreal
country: Canada
state: Quebec
city: Quebec City
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
Study officials:
affiliation: University of Wisconsin, Madison
name: Minesh P Mehta, MD
role: STUDY_CHAIR
References:
citation: Mehta MP, Rodrigus P, Terhaard CH, Rao A, Suh J, Roa W, Souhami L, Bezjak A, Leibenhaut M, Komaki R, Schultz C, Timmerman R, Curran W, Smith J, Phan SC, Miller RA, Renschler MF. Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases. J Clin Oncol. 2003 Jul 1;21(13):2529-36. doi: 10.1200/JCO.2003.12.122.
citation: Evens AM. Motexafin gadolinium: a redox-active tumor selective agent for the treatment of cancer. Curr Opin Oncol. 2004 Nov;16(6):576-80. doi: 10.1097/01.cco.0000142073.29850.98.
citation: Biaglow JE, Miller RA. The thioredoxin reductase/thioredoxin system: novel redox targets for cancer therapy. Cancer Biol Ther. 2005 Jan;4(1):6-13. doi: 10.4161/cbt.4.1.1434. Epub 2004 Jan 8.
citation: Manon R, Hui S, Chinnaiyan P, Suh J, Chang E, Timmerman R, Phan S, Das R, Mehta M. The impact of mid-treatment MRI on defining boost volumes in the radiation treatment of glioblastoma multiforme. Technol Cancer Res Treat. 2004 Jun;3(3):303-7. doi: 10.1177/153303460400300308.
citation: Meyers CA, Smith JA, Bezjak A, Mehta MP, Liebmann J, Illidge T, Kunkler I, Caudrelier JM, Eisenberg PD, Meerwaldt J, Siemers R, Carrie C, Gaspar LE, Curran W, Phan SC, Miller RA, Renschler MF. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol. 2004 Jan 1;22(1):157-65. doi: 10.1200/JCO.2004.05.128.