Clinical trial NCT00717275: Study of Temozolomide to Treat Newly Diagnosed Brain Metastases
Official title: A Phase II Study of Temozolomide (TMZ) Following Stereotactic Radiosurgery (SRS) for Patients With Newly Diagnosed Brain Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Brain Metastases
Keywords: Brain Metastases
Temozolomide
Temodar
TMZ
Stereotactic Radiosurgery
SRS
Lead sponsor: University of Florida
Sponsor class: OTHER
First posted: 2008-07-17
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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

Primary outcomes:
measure: Number of Participants Who Developed Distant Brain Failure at One Year.
timeFrame: 1 Year
Secondary outcomes:
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: University of Florida
name: Erin M Dunbar, MD
role: PRINCIPAL_INVESTIGATOR
References: