2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

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

Treatments: Drug: 2-methoxyestradiol; Other: laboratory biomarker analysis; Other: pharmacological study

Study type: Interventional

Funder types: NIH

Identifiers

NCT00028821

U01CA069912 (U.S. NIH Grant/Contract)

NCI-2012-02439

CDR0000069137 (Registry Identifier)

MC0017

Details and patient eligibility

About

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

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Treatment (2-methoxyestradiol)

Experimental group

Description:

Patients receive oral 2-methoxyestradiol (2-ME) once daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Other: pharmacological study

Drug: 2-methoxyestradiol

Other: laboratory biomarker analysis