2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00028821
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : January 16, 2013
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
Phase I trial to study the effectiveness of 2-methoxyestradiol in treating patients who have advanced solid tumors. 2-methoxyestradiol may stop or slow the growth of solid tumors by stopping blood flow to the tumor

Condition or disease Intervention/treatment Phase
Refractory Multiple Myeloma Stage III Multiple Myeloma Unspecified Adult Solid Tumor, Protocol Specific Drug: 2-methoxyestradiol Other: pharmacological study Other: laboratory biomarker analysis Phase 1

Detailed Description:


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 : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I and Pharmacologic Study of 2-Methoxyestradiol in Patients With Advanced Solid Tumors
Study Start Date : January 2002
Actual Primary Completion Date : April 2006

Resource links provided by the National Library of Medicine

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.
Drug: 2-methoxyestradiol
Given orally
Other Names:
  • 2-ME
  • 2-Methoxy Estradiol
  • 2ME2
  • Panzem

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. 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.

  2. 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.

Secondary Outcome Measures :
  1. 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.

  2. Angiogenesis inhibition via an ex vivo angiogenesis assay [ Time Frame: At day 1 and at day 28 ]
    The relationship between each marker and dose level will be explored descriptively.

  3. Number of responses [ Time Frame: Up to 3 months after completion of treatment ]
    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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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00028821

United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Charles Erlichman Mayo Clinic

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00028821     History of Changes
Other Study ID Numbers: NCI-2012-02439
U01CA069912 ( U.S. NIH Grant/Contract )
CDR0000069137 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: January 16, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs