Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI MAYO-MC0017 NCI-3356, NCT00028821, 3356

Objectives

1. Determine the optimal biologic dose and/or maximum tolerated dose of 2-methoxyestradiol in patients with advanced solid tumors.
2. Determine the qualitative and quantitative toxic effects of this drug in these patients.
3. Determine the pharmacokinetics and metabolism of this drug in these patients.
4. Determine the biologic changes within the tumor of these patients when treated with this drug.
5. Correlate the pharmacokinetics and toxicity of this drug in these patients.
6. Evaluate the biologic evidence of angiogenesis inhibition in patients receiving this drug.
7. Correlate genetic polymorphisms in cytochrome P450 and sulfotransferases isoforms with the pharmacokinetics of this drug.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy:

• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior immunotherapy
• No concurrent immunotherapy

Chemotherapy:

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent megestrol

Radiotherapy:

• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 25% of bone marrow
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics
• No prior extensive resection of terminal small bowel
• No prior major resection of the stomach or proximal small bowel

Other:

• No other concurrent ancillary investigational therapy

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 10.0 g/dL

Hepatic:

• Bilirubin normal
• AST no greater than 2.5 times upper limit of normal (ULN)

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Gastrointestinal:

• 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

Other:

• 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

Expected Enrollment

A total of 42-60 patients will be accrued for this study within 19 months.

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.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Charles Erlichman, MD, Protocol chair		Ph: 507-284-2511 Email: erlichman.charles@mayo.edu

Registry Information
Official Title		A Phase I and Pharmacologic Study of 2-Methoxyestradiol in Patients with Advanced Solid Tumors
Trial Start Date		2002-01-03
Registered in ClinicalTrials.gov		NCT00028821
Date Submitted to PDQ		2001-11-09
Information Last Verified		2006-05-03
NCI Grant/Contract Number		P30-CA15083, U10-CA69912

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