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About
RATIONALE: Osmotic blood-brain barrier disruption uses certain drugs, such as mannitol, to open the blood vessels around the brain and allow tumor-killing substances to be carried directly to the brain. Drugs used in chemotherapy, such as methotrexate and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Trastuzumab may also help methotrexate and carboplatin work better by making tumor cells more sensitive to the drugs. Giving osmotic blood-brain barrier disruption together with methotrexate, carboplatin, and trastuzumab may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of carboplatin when given together with methotrexate and trastuzumab after mannitol in treating women with breast cancer that has spread to the brain.
Full description
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, phase I, pilot, dose-finding study of carboplatin followed by a phase II, open-label study.
Cohorts of 3-6 patients receive decreasing doses of carboplatin and/or methotrexate if the proposed dose is not well tolerated. Dose-limiting toxicity is defined as grade IV hematologic toxicity with delay in subsequent treatment courses for 4 weeks OR grade III/IV nonhematologic toxicity without recovery in 14 days during the course of treatment.
Neuropsychological assessment is performed at baseline, every 6 months during treatment, every 6 months for 1 year, and then annually thereafter. Quality of life is assessed at baseline, every 3 months during treatment, at the completion of study treatment, every 6 months for 1 year, and then annually thereafter.
After completion of study therapy, patients are followed periodically.
PROJECTED ACCRUAL: A total of 78 patients will be accrued for this study.
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Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
PATIENT CHARACTERISTICS:
Female
Menopausal status not specified
ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 6 weeks
Hematocrit ≥ 25%
WBC ≥ 2,500/mm³
Absolute neutrophil count ≥ 1,200/mm³
Platelet count ≥100,000/mm³
Creatinine clearance ≥ 50 mL/min (eligible for full-dose methotrexate) (30-49 mL/min allowed for patients receiving reduced-dose methotrexate)
Bilirubin ≤ 2.0 times upper limit of normal
LVEF normal by echocardiogram or MUGA
Adequate pulmonary and cardiac function to tolerate general anesthesia as determined by physical examination and history
No New York Heart Association class III-IV heart disease
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No known allergy to trastuzumab (HER2-positive patients), carboplatin, methotrexate, or sodium thiosulfate
No hepatitis B or C positivity
No uncontrolled intercurrent illness including, but not limited to, any of the following:
PRIOR CONCURRENT THERAPY:
Primary purpose
Allocation
Interventional model
Masking
0 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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