2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase I and Pharmacologic Study of 2-Methoxyestradiol in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00028821
• Other study ID #: NCI-2012-02439
• Secondary ID: MC0017U01CA06991
• Status: Completed
• Phase: Phase 1
• First received: January 4, 2002
• Last updated: January 15, 2013
• Start date: January 2002

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. primary completion date: April 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Stage III Multiple Myeloma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• 2-methoxyestradiol
Given orally

Other:
• pharmacological study
Correlative studies
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by Common Toxicity Criteria (CTC) version 2.0	Presented primarily in a descriptive fashion.	28 days	Yes
Primary	Number of toxicity incidents as assessed by CTC version 2.0	Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.	Up to 3 months after completion of treatment	Yes
Secondary	Biologic activity rate (BAR)	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.	At day 1 and at day 28	No
Secondary	Angiogenesis inhibition via an ex vivo angiogenesis assay	The relationship between each marker and dose level will be explored descriptively.	At day 1 and at day 28	No
Secondary	Number of responses	Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease.	Up to 3 months after completion of treatment	No