2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00028821

Last Updated: 2013-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31

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

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.

Conditions

Refractory Multiple Myeloma; Stage III Multiple Myeloma; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

2-methoxyestradiol

Intervention Type: DRUG

Given orally

pharmacological study

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

2-methoxyestradiol

Given orally

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

2-ME; 2-Methoxy Estradiol; 2ME2; Panzem; pharmacological studies

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Erlichman

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

MC0017

Identifier Type: -

Identifier Source: secondary_id

U01CA069912

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000069137

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02439

Identifier Type: -

Identifier Source: org_study_id