- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00028821
2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors
A Phase I and Pharmacologic Study of 2-Methoxyestradiol in Patients With Advanced Solid Tumors
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (2-methoxyestradiol)
Patients receive oral 2-methoxyestradiol (2-ME) once daily.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Correlative studies
Other Names:
Given orally
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by Common Toxicity Criteria (CTC) version 2.0
Time Frame: 28 days
|
Presented primarily in a descriptive fashion.
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28 days
|
Number of toxicity incidents as assessed by CTC version 2.0
Time Frame: Up to 3 months after completion of treatment
|
Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.
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Up to 3 months after completion of treatment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biologic activity rate (BAR)
Time Frame: At day 1 and at day 28
|
A rate will be calculated by dividing the number of patients with BA by the number of patients treated at the phase II recommended dose level.
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At day 1 and at day 28
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Angiogenesis inhibition via an ex vivo angiogenesis assay
Time Frame: At day 1 and at day 28
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The relationship between each marker and dose level will be explored descriptively.
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At day 1 and at day 28
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Number of responses
Time Frame: Up to 3 months after completion of treatment
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Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.
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Up to 3 months after completion of treatment
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Estrogens
- Estradiol
- 2-Methoxyestradiol
Other Study ID Numbers
- NCI-2012-02439
- U01CA069912 (U.S. NIH Grant/Contract)
- MC0017
- CDR0000069137 (REGISTRY: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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