2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00030095

Last Updated: 2015-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-09-30

Brief Summary

RATIONALE: 2-Methoxyestradiol may stop the growth of cancer 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.

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of 2-methoxyestradiol in patients with advanced solid tumors.
• Determine the side effect profile of this drug in these patients.
• Determine the pharmacokinetic profile of this drug in these patients.
• Determine the changes in positron-emission tomography scans of patients treated with this drug.
• Determine the changes in apotosis in patients treated with this drug.

OUTLINE: This is a dose-escalation study.

Patients receive oral 2-methoxyestradiol (2ME2) once on day 1 followed by 2 days of evaluation. Patients then receive oral 2ME2 every 12 hours. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 2ME2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at day 30.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 1 year.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Primary Study Purpose: TREATMENT

Interventions

2-methoxyestradiol

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor

• Metastatic or unresectable disease for which standard curative treatments do not exist or are no longer effective
• Clinically progressive disease documented by any of the following:

• New area of malignant disease
• Progression of soft-tissue metastases
• At least 1 new metastatic deposit on technetium Tc 99m bone scintigraphy
• Increases in prostate-specific antigen
• Lesions accessible for serial biopsy
• No known brain metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin normal
• AST/ALT no greater than 2.5 times upper limit of normal

Renal:

• Creatinine normal OR
• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other:

• No other concurrent uncontrolled illness
• No ongoing or active infection
• No prior allergic reactions to compounds of similar chemical or biological composition to 2-methoxyestradiol
• No psychiatric illness or social situation that would preclude study compliance
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception for 1 month before, during, and for 1 month after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior biologic therapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for mitomycin, nitrosoureas, or carboplatin)
• No concurrent chemotherapy for cancer

Endocrine therapy:

• Luteinizing-hormone releasing-hormone agonist therapy must be continued for patients with prostate cancer except those with prior orchiectomy

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy for cancer

Surgery:

• See Endocrine therapy

Other:

• Recovered from prior therapy
• No other concurrent therapy for cancer
• No concurrent combination antiretroviral therapy for HIV-positive patients

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

William Dahut, MD

Role: STUDY_CHAIR

NCI - Medical Oncology Branch

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

NCI - Center for Cancer Research

Bethesda, Maryland, United States

Countries

United States

References

Lakhani NJ, Sarkar MA, Venitz J, Figg WD. 2-Methoxyestradiol, a promising anticancer agent. Pharmacotherapy. 2003 Feb;23(2):165-72. doi: 10.1592/phco.23.2.165.32088.

Reference Type: BACKGROUND

PMID: 12587805 (View on PubMed)

Lakhani NJ, Sparreboom A, Venitz J, et al.: Single oral dose pharmacokinetics (PK) and safety of 2-methoxyestradiol (2ME2) in patients with solid tumors. [Abstract] J Clin Oncol 23 (Suppl 16): A-2071, 152s, 2005.

Reference Type: RESULT

Dahut WL, Lakhani N, Kohn EC, et al.: A phase I study of 2-methoxyestradiol (2ME2) in patients with solid tumors. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-833, 2003.

Reference Type: RESULT

Other Identifiers

NCI-01-C-0256

Identifier Type: -

Identifier Source: secondary_id

NCI-3371

Identifier Type: -

Identifier Source: secondary_id

NCI-CC-01-C-0256

Identifier Type: -

Identifier Source: secondary_id

CDR0000069022

Identifier Type: -

Identifier Source: org_study_id

NCT00024609

Identifier Type: -

Identifier Source: nct_alias