Study of Temozolomide to Treat Newly Diagnosed Brain Metastases
Condition: Brain Metastases
MeSH terms: Neoplasm Metastasis; Brain Neoplasms
Intervention: Temozolomide
Intervention description: 75 mg/m2 taken by mouth once a day for 14 out of 28 consecutive days until progression or unacceptable toxicity.
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Brain Metastases; Temozolomide; Temodar; TMZ; Stereotactic Radiosurgery; SRS

Summary:

      The purpose of this study is to determine if administering temozolomide after completion of
      stereotactic radiosurgery helps control existing brain metastases and prevents the
      developement of new brain metastases.
    

Eligibility criteria:

        Inclusion Criteria:

        Tumor characteristics adequate for stereotactic radiosurgery:

          1. 1-3 newly diagnosed, previously untreated, brain metastases

          2. Each tumor measuring a size less than or equal to 3 cm

          3. No other contraindications to stereotactic radiosurgery

        Systemic parameters adequate for temozolomide following stereotactic radiosurgery:

          1. Histological confirmation of systemic malignancy (brain confirmation not required)

          2. Male or female 18 years of age or older

          3. Negative pregnancy test (if of childbearing potential)

          4. Any number of previous recurrences will be allowed

          5. Karnofsky Performance Status > 60

          6. Hematocrit > 30,000

          7. White blood cell count > 1,500

          8. Platelet > 100,000

          9. Absolute Neutrophil Count > 1,000

         10. Bilirubin < 1.5 x upper limits of normal

         11. Transaminases (ALT and AST) < 1.5 x upper limits of normal

         12. Creatinine < 1.5 x upper limits of normal

         13. Adequate medical health to participate in this study

         14. Adequate documentation of menopause (natural/surgical) or patient commitment to
             routine use of reliable birth control (barrier/hormonal)

         15. Ability to read and understand the informed consent document

         16. Ability and willingness to follow all requirements of the study including following
             all directions, taking medication as prescribed and completing all diaries and forms

         17. No other contraindications to temozolomide (severe organ dysfunction,
             immunosuppression, etc.)

         18. Medical stability and/or recovery from effects of stereotactic radiosurgery

        Exclusion Criteria:

          1. Karnofsky Performance Status < 60

          2. Hematocrit < 30,000

          3. White blood cell count < 1,500

          4. Platelet < 100,000

          5. Absolute Neutrophil Count < 1,000

          6. Bilirubin >1.5 x upper limits of normal

          7. Transaminases (ALT and AST) > 1.5 x upper limits of normal

          8. Creatinine > 1.5 x upper limits of normal

          9. Inability to undergo gadolinium-contrasted MRIs, including severe claustrophobia or
             insufficient allergy prophylaxis

         10. Germ cell, leukemia, and lymphoma histologies will be excluded

         11. Prior chemotherapy or radiotherapy for brain metastases (prior resection and steroids
             are allowed)

         12. Contraindications to radiosurgery or temozolomide chemotherapy

         13. Uncontrolled systemic malignancy

         14. Chemotherapy or other systemic therapy for systemic malignancy within a specified time
             of temozolomide initiation, depending on half-life of agent:

               1. Cytotoxic chemotherapy within the previous 4 weeks

               2. Nitrosurea (CCNU, BCNU) within the previous 6 weeks

               3. Gliadel or temozolomide within the previous 4 weeks

               4. Bevacizumab or other antiangiogenic agent within the previous 4 weeks

               5. Other targeted molecular or antibody agent within the previous 4 weeks

               6. Hormonal agent within the previous 2 weeks