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2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00028821
First received: January 4, 2002
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

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: Endpoint Classification: Pharmacokinetics/Dynamics Study
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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00028821

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Charles Erlichman Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00028821     History of Changes
Other Study ID Numbers: NCI-2012-02439, MC0017, U01CA069912, CDR0000069137
Study First Received: January 4, 2002
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on November 23, 2014