RATIONALE: 2-methoxyestradiol may stop or slow the growth of solid tumors by stopping blood flow to the tumor.

PURPOSE: Phase I trial to study the effectiveness of 2-methoxyestradiol in treating patients who have advanced solid tumors.

Condition	Treatment or Intervention	Phase
refractory plasma cell neoplasm stage III multiple myeloma unspecified adult solid tumor, protocol specific	Drug: 2-methoxyestradiol  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: growth factor antagonist therapy	Phase I

OBJECTIVES:

• Determine the optimal biologic dose and/or maximum tolerated dose of 2-methoxyestradiol in patients with advanced solid tumors.
• Determine the qualitative and quantitative toxic effects of this drug in these patients.
• Determine the pharmacokinetics and metabolism of this drug in these patients.
• Determine the biologic changes within the tumor of these patients when treated with this drug.
• Correlate the pharmacokinetics and toxicity of this drug in these patients.
• Evaluate the biologic evidence of angiogenesis inhibition in patients receiving this drug.
• 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 above,  Genders Eligible for Study:  Both

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

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/mm^3
• Platelet count at least 100,000/mm^3
• 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

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

Minnesota
      Mayo Clinic Cancer Center, Rochester,  Minnesota,  55905,  United States; Recruiting

Study chairs or principal investigators

Charles Erlichman, MD,  Study Chair,  Mayo Clinic Cancer Center   

Study ID Numbers:  CDR0000069137; MAYO-MC0017; NCI-3356
Record last reviewed:  July 2002
Record first received:  January 4, 2002
ClinicalTrials.gov Identifier:  NCT00028821
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-22