Phase II Study of Gamma Knife Radiosurgery and Temozolomide for Brain Metastases
Condition: Cancer; Brain Metastases
MeSH terms: Neoplasm Metastasis; Brain Neoplasms
Intervention: temozolomide
Intervention description: TMZ 200mg/m2 days 1-5 repeat q28 days. Patients who have received prior chemotherapy will receive 150 mg/m2 days 1-5
Intervention MeSH terms: Temozolomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 19 Years
Healthy volunteers: No
Keywords: Cancer; Brain metastases; Gamma Knife Radiosurgery; Temodar; Temozolomide

Summary:

      The protocol is designed to determine the efficacy of temozolomide in preventing the
      development of new brain metastases within the first year in patients undergoing stereotactic
      radiation for newly diagnosed brain metastases.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All subjects must have history of histologically confirmed malignancy. Brain biopsy is
             not required unless diagnosis is judged to be in doubt by the treating physician.

          -  Newly diagnosed brain metastases (four or fewer by thin slice post-contrast MRI).

          -  ECOG performance status of less than or equal to 2 for patients with no prior
             chemotherapy, and less than or equal to 1 for patients with prior chemotherapy.

          -  Age greater than 18

          -  Life expectancy greater than 12 weeks

          -  Subjects given written informed consent

          -  Adequate hematologic, renal and liver function as demonstrated by laboratory values
             performed within 14 days, inclusive, prior to administration of study drug:

               -  Absolute neutrophil count (ANC) >= 1500/mm3

               -  Platelet count >= 100,000/mm3

               -  Hemoglobin >= 9 g/dL

               -  BUN and serum creatinine <= 1.5 times upper limit of laboratory normal

               -  Total and direct bilirubin <= 2 times upper limit of laboratory normal or in the
                  presence of documented liver metastases, total and direct bilirubin <=5 times
                  upper limit of normal

               -  SGOT and SGPT <= 2 times upper limit of laboratory normal or in the presence of
                  documented liver metastases, SGOT and SGPT <=5 times upper limit of normal

               -  Alkaline phosphatase <= 2 times upper limit of laboratory normal or in the
                  presence of documented liver metastases, alkaline phosphatase of <= 5 times upper
                  limit of normal

        Exclusion Criteria:

          -  Patients with small cell lung cancer and lymphoma are ineligible.

          -  More than four metastases by thin slice MRI. Note that if a diagnostic study prior to
             radiosurgery demonstrates only four tumors but the gamma knife treatment-planning scan
             reveals greater than four tumors, the patients will still be eligible for the protocol
             if all tumors can be treated with radiosurgery.

          -  Chemotherapy within four weeks prior to study drug administration

          -  Patients, who in the opinion of the treating medical oncologist, require immediate
             cytotoxic chemotherapy other than the study drug. Allowed medications include
             antihormonal agents (i.e., Tamoxifen), herceptin and bisphosphonates.

          -  Radiation therapy to greater than or equal to 50% of the bone marrow. Completion of
             radiation therapy less than 4 weeks prior to study drug administration for
             radiotherapy to >= 15% of bone marrow and less than 2 weeks prior for radiotherapy to
             < 15% of bone marrow.

          -  Insufficient recovery from all active toxicities of prior therapies

          -  Subjects who are poor medical risks because of non-malignant systemic disease

          -  Frequent vomiting or medical condition that could interfere with oral medication
             intake (e.g., partial bowel obstruction).

          -  Previous or concurrent malignancies at other sites, or treatment for malignancy at the
             site within 5 years of study start with the exception of surgically cured carcinoma
             in-situ of the cervix and basal or squamous cell carcinoma of the skin.

          -  Known HIV positively or AIDS-related illness.

          -  Pregnant or nursing women.

          -  Women of childbearing potential who are not using an effective method of
             contraception. Women of childbearing potential must have a negative serum pregnancy
             test 24 hours prior to administration of study drug and be practicing medically
             approved contraceptive precautions.

          -  Men who are not advised to use an effective method of contraception.