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2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors

This study has been completed.
Information provided by (Responsible Party):
National Cancer Institute (NCI) Identifier:
First received: January 4, 2002
Last updated: January 15, 2013
Last verified: January 2013
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 Intervention 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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I and Pharmacologic Study of 2-Methoxyestradiol in Patients With Advanced Solid Tumors

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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.

  • 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:
  • 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.

  • 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.

  • 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.

Enrollment: 60
Study Start Date: January 2002
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
  Contacts and Locations
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Please refer to this study by its identifier: NCT00028821

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

Responsible Party: National Cancer Institute (NCI) Identifier: NCT00028821     History of Changes
Other Study ID Numbers: NCI-2012-02439
U01CA069912 ( US NIH Grant/Contract Award Number )
CDR0000069137 ( Registry Identifier: PDQ (Physician Data Query) )
Study First Received: January 4, 2002
Last Updated: January 15, 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 processed this record on April 28, 2017