A Phase I and Pharmacologic Study of 2-Methoxyestradiol in Patients With Advanced Solid Tumors
18 Years
N/A
Both
Refractory Multiple Myeloma, Stage III Multiple Myeloma, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I and Pharmacologic Study of 2-Methoxyestradiol in Patients With Advanced Solid Tumors
PRIMARY OBJECTIVES:
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
drug.
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
MTD.
Patients are followed for 3 months.
PROJECTED ACCRUAL: A total of 42-60 patients will be accrued for this study within 19
months.
Inclusion Criteria:
- Histologically confirmed solid tumor that is clinically unresectable
- No known standard therapy that is potentially curative or definitely capable of
extending life expectancy
- Patients with multiple myeloma may be enrolled to expansion cohort once the
recommended phase II dose is established
- Tumor amenable to serial biopsy
- No bone metastases as only site of disease
- No CNS metastases
- Performance status - ECOG 0-2
- At least 12 weeks
- Absolute neutrophil count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 10.0 g/dL
- Bilirubin normal
- AST no greater than 2.5 times upper limit of normal (ULN)
- Creatinine no greater than 1.5 times ULN
- No New York Heart Association class III or IV heart disease
- Adequate oral intake
- No malabsorption syndrome
- No disease of terminal small bowel
- No dysphagia or other condition that would interfere with ability to swallow intact
capsules
- No clinical contraindications (e.g., anticoagulant therapy) to biopsy
- No uncontrolled infection
- No seizure disorder
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- More than 4 weeks since prior biologic therapy
- More than 4 weeks since prior immunotherapy
- No concurrent immunotherapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered
- No concurrent chemotherapy
- No concurrent megestrol
- More than 4 weeks since prior radiotherapy
- No prior radiotherapy to more than 25% of bone marrow
- No concurrent radiotherapy
- No prior extensive resection of terminal small bowel
- No prior major resection of the stomach or proximal small bowel
- No other concurrent ancillary investigational therapy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by Common Toxicity Criteria (CTC) version 2.0
Outcome Description:
Presented primarily in a descriptive fashion.
Outcome Time Frame:
28 days
Safety Issue:
Yes
Principal Investigator
Charles Erlichman
Investigator Role:
Principal Investigator
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02439
NCT ID:
NCT00028821
Start Date:
January 2002
Completion Date:
Related Keywords:
- Refractory Multiple Myeloma
- Stage III Multiple Myeloma
- Unspecified Adult Solid Tumor, Protocol Specific
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Neoplasms
Name | Location |
|---|---|
| Mayo Clinic | Rochester, Minnesota 55905 |
