A Phase I and Pharmacologic Study of 2-Methoxyestradiol in Patients With Advanced Solid Tumors
I. Determine the optimal biologic dose and/or maximum tolerated dose of 2-methoxyestradiol
in patients with advanced solid tumors.
II. Determine the qualitative and quantitative toxic effects of this drug in these patients.
III. Determine the pharmacokinetics and metabolism of this drug in these patients.
IV. Determine the biologic changes within the tumor of these patients when treated with this
V. Correlate the pharmacokinetics and toxicity of this drug in these patients. VI. Evaluate
the biologic evidence of angiogenesis inhibition in patients receiving this drug.
VII. Correlate genetic polymorphisms in cytochrome P450 and sulfotransferases isoforms with
the pharmacokinetics of this drug.
OUTLINE: This is a dose-escalation study.
Patients receive oral 2-methoxyestradiol (2-ME) once daily. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of 2-ME until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3
or 2 of 6 patients experience dose-limiting toxicity. Additional patients are treated at the
Patients are followed for 3 months.
PROJECTED ACCRUAL: A total of 42-60 patients will be accrued for this study within 19
Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by Common Toxicity Criteria (CTC) version 2.0
Presented primarily in a descriptive fashion.
United States: Food and Drug Administration
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