Study of Temozolomide to Treat Newly Diagnosed Brain Metastases

Study Overview
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Brief Summary
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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.

Detailed Description
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Brain metastases represent a heterogenous group of system tumors whose presence in the central nervous system result in profound neurological devastation. Existing therapies for brain metastases are focused on improving both neurologic function and survival. Therapies aimed at controlling the tumor both at the site of the brain metastases and the rest of the brain have the potential to improve outcomes and quality of life. The combined use of stereotactic radiosurgery followed by temozolomide may represent such a strategy.

Official Title
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A Phase II Study of Temozolomide (TMZ) Following Stereotactic Radiosurgery (SRS) for Patients With Newly Diagnosed Brain Metastases

Conditions
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Brain Metastases

Intervention / Treatment
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* Drug: Temozolomide


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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Temozolomide<br> | Drug: Temozolomide<br>* 75 mg/m2 taken by mouth once a day for 14 out of 28 consecutive days until progression or unacceptable toxicity.<br>* Other names: TMZ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Developed Distant Brain Failure at One Year. |  | 1 Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMZ, Brain Metastases, Temozolomide, Temodar, Stereotactic Radiosurgery, SRS