PCYC-0224 - PHASE II TRIAL OF MOTEXAFIN GADOLINIUM WITH WHOLE BRAIN RADIATION THERAPY (WBRT) FOLLOWED BY STEREOTACTIC RADIOSURGERY BOOST IN THE TREATMENT OF PATIENTS WITH BRAIN METASTASES
Principal Investigator: Robert Timmerman, MD
Coordinator: Candice Price, RN 
Contact Number: (214) 648-5536

Primary Endpoint: Rate of irreversible Grade 3 or any Grade 4 or 5 neurologic radiation toxicities occurring within 3 months following SRS boost.
Study Population: Approximately 45 adult patients with 1 to 4 brain metastases from solid tumors and good KPS (greater than or equal to 70).

Treatment Schedule:

• WBRT 2.5Gy/day x 15 treatment days (37.5Gy) plus MGd 5mg/kg IV, 2-5 hours before WBRT fractions 6-15
• SRS boost within 14 days of last WBRT plus MGd 5mg/kg IV, at least 2 hours before SRS

Visit Schedule: Screening visit can occur up to 14 days prior to initiation of WBRT and as late as Day 5 of WBRT administration.
Follow-up: Monthly through Month 9 (from start of WBRT) and in 3-month intervals thereafter. Confirmatory visit 2 to 3 weeks after neurologic deterioration. Visits are to continue until the last patient's scheduled Month 6 follow-up visit.

Screening Assessment:

• History, physical, KPS, and weight
• Neurological exam & symptoms
• Neurocognitive testing
• CBC and serum chemistry
• Serum pregnancy test (for women of childbearing potential)

INCLUSION CRITERIA:

• Age: 18 years or older
• KPS: 70 or greater
• Histologically confirmed malignancy with the  presence of 1 to 4 intraparenchymal brain metastases.
• Diagnostic gadolinium contrast-enhanced MRI demonstrating the presence of 1 to 4 unresected brain metastases performed within 30 days prior to enrollment.
• The contrast-enhancing tumor must be well circumscribed and must have a maximum diameter less than or equal to 4.0 cm in any direction on the enhanced scan. If multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0 cm in maximum diameter.

EXCLUSION CRITERIA:

• Previous cranial radiation.
• Complete resection of all known brain metastases.
• Leptomeningeal metastases documented by MRI or cerebral spinal fluid (CSF) evaluation (lumbar puncture not required).
• Liver metastases (re-staging not required).
• Clinical or radiologic evidence of progression (other than study lesion[s]) within 1 month prior to enrollment.
• Metastases within 10 mm of the optic apparatus so that some portion of the optic nerve or chiasm would be included in the high dose SRS boost field.
• Metastases in the brainstem, midbrain, pons, or medulla.
• Planned chemotherapy during WBRT and/or SRS (prior and subsequent chemotherapy is allowed).
• Uncontrolled hypertension (defined as systolic blood pressure > 160 mm Hg and diastolic blood pressure > 110 mm Hg on maximum medical therapy).
• Laboratory values as follows:
  *  Lactate dehydrogenase (LDH) > 1.3 x ULN
  *  Absolute neutrophil count (ANC) < 1500/mm3
  *  Platelets < 50,000/mm3
  *  Creatinine > 2.0 mg/dL
  *  AST or ALT > 3 x ULN.
  *  Total bilirubin > 2 x ULN
• Women who are pregnant or lactating.