2-Methoxyestradiol (2-ME2) to Treat Solid Tumor Cancers
This study is no longer recruiting patients.
Purpose
This study will determine the safest dose of 2-methoxyestradiol (2-ME2) that can be given to cancer patients. 2-ME2 has reduced
the growth of both primary and metastatic (spreading) human tumors in mice. The drug is thought to prevent or slow the growth
of blood vessels that supply tumors.
Patients 18 years of age or older with a solid tumor cancer that has spread from the primary site or cannot be removed surgically
and for which standard treatments are no longer effective may be eligible for this study. Patients with metastatic brain
tumors are excluded. Candidates will be screened with studies such as computed tomography (CT) scans to determine the extent
of spread of the cancer, blood and urine tests. This evaluation may take up to 2 weeks to complete.
Participants will be hospitalized for the first dose of 2-ME2. This dose will be followed by blood sampling (about 14 samples
of 1 teaspoon each over 2 days) to determine how much of the drug enters the blood. Patients will then take 2-ME2 at home
twice a day for 6 months or more, depending on their response to the drug. They will be followed at NIH every 2 weeks for
12 weeks after starting therapy and then monthly. In addition, participants will undergo the following procedures:
Biopsies-removal of a small piece of tumor for study under the microscope-are done before starting therapy and again after
1 to 2 months.
Standard X-rays are taken before starting therapy and then every 2 months.
Computed tomography (CT) scans, which use X-rays to provide 3-dimensional images of the part of the body being studied, are
done after 2 months and then every 2 months.
Positron emission tomography (PET), a test are similar to CT, but which uses an injected or ingested radioactive material
to produce images, is done before starting therapy and several months later. PET scans can help determine if 2-ME is blocking
blood vessel growth to the tumor.
Blood tests are done with each clinic visit to determine the effects of 2-ME2 on blood counts and liver and kidney function,
and then monthly to measure the concentration of the drug in the body and look for factors associated with the cancer.
Some patients may also have magnetic resonance imaging (MRI), which uses radio waves and a magnetic field to produce images
of the structure and function of various tissues; ultrasound (using sound waves to produce images); or a bone scan to measure
tumor extent.
Condition
|
Treatment or Intervention |
Phase |
Pathologic Angiogenesis Neoplasm
|
Drug: 2ME2
|
Phase I
|
MedlinePlus related topics: Cancer; Cancer Alternative Therapy
Study Type: Interventional
Study Design: Treatment, Safety
Official Title: Phase I Trial of 2-Methoxyestradiol (2ME2), (NSC-659853) an Angiogenesis Inhibitor, in Patients with Solid Tumors
Further Study Details:
Expected Total Enrollment:
30
Study start: September 17, 2001
2-Methoxyestradiol (2ME2) is an antiangiogenic and antiproliferative human metabolite of estradiol. 2ME2 inhibits endothelial
cell proliferation and in vitro angiogenesis. In addition, 2ME2 has been shown to enhance tumor cell apoptosis and bind to
tubulin. This is a dose-escalation phase I study of 2ME2, an oral angiogenesis inhibitor, in patients with solid tumors.
The endpoints of this trial are to: 1) determine the maximum tolerated dose (MTD) of 2ME2, 2) characterize the toxicity
profile of 2ME2, 3) characterize the pharmacokinetics of 2ME2. We will be looking at molecular/biological endpoints, in particular,
the effect of 2ME2 on PET imaging (O(15) and FDG), and the effect of 2ME2 on apoptosis (either endothelial cells or epithelial
cells).
Eligibility
Genders Eligible for Study:
Both
INCLUSION CRITERIA:
Patients must have histologically confirmed solid malignancy that is metastatic or unresectable and for which standard curative
measures do not exist or are no longer effective.
Patients must have histopathological documentation of cancer confirmed in the Laboratory of Pathology/NCI of the Clinical
Center at the National Institutes of Health or the Department of Pathology at the NNMC prior to starting this study (a block
of primary tissue from the time of diagnosis will be requested on each patient).
Patients must have clinically progressive disease documented prior to entry. Progression must be documented by at least one
of the following parameters: Development of new area of malignant disease (measurable or evaluable); Progression of soft-tissue
metastases as measured by appropriate modalities (i.e. imaging, palpation); and/or at least one new metastatic deposit on
Tc-99 bone scintigraphy; and/or increases in PSA per Consensus Guidelines
ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%)
Patients must have a life expectancy of more than 3 months.
Patients must have normal organ and marrow function as defined below (obtained within 4 days of enrollment): Leukocytes greater
than or equal to 3,000/microliters, Absolute neutrophil count greater than or equal to 1,500/microliters, Platelets greater
than or equal to 100,000/microliters, Total bilirubin within normal institutional limits, AST(SGOT)/ALT(SGPT) less than or
equal to 2.5 X institutional upper limit of normal within normal institutional limits, Creatinine within normal institutional
limits OR creatinine clearance greater than or equal to 60 ml/min for patients with creatinine levels above institutional
normal.
Patients must have recovered from any acute toxicity related to prior therapy.
Patients must be off prior chemotherapy, radiation therapy, or biological therapy for at least 4 weeks prior to initiation
of 2ME2. Patients who were receiving mitomycin C, nitrosoureas, or carboplatin must be 6 weeks from the last administration
of chemotherapy. Patients with prostate cancer must continue to receive LHRH agonist (unless orchiectomy has been done).
Patients must be willing to travel from their home to the NIH for follow-up visits.
The effects of 2ME2 on the developing human fetus are unknown. Women of child-bearing potential and men must agree to use
adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or
suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Patients must be able to understand and sign the attached informed consent form. Patients will be offered the opportunity
to sign a durable Power of Attorney.
Patients must be greater than or equal to 18 years of age.
All patients in each dose level must have biopsiable lesions for serial biopsy, and be willing to participate in their correlative
studies.
All patients must be willing to participate in the PET imaging study #98-C-0163 The Use of Positron Emission Tomography (PET)
and Magnetic Resonance Imaging (MRI) to Assess the Effects of Antineoplastic Therapy on Tumor Associated Vasculature.
EXCLUSION CRITERIA:
Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they
often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
Concurrent therapy for their cancer (i.e., radiation therapy, chemotherapy, etc. except LHRH which patients with prostate
cancer must continue).
Pregnant women are excluded from this study because 2ME2 has anti-angiogenic properties with the potential for teratogenic
or abortifacient effects. In addition, because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with 2ME2, breastfeeding should be discontinued if the mother is treated with 2ME2.
HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic
interactions with 2ME2 or other agents administered during the study.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to 2ME2 or other agents
used in study.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active severe infection, symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance
with study requirements.
Location
Information
Maryland National Cancer Institute (NCI), 9000 Rockville Pike,
Bethesda,
Maryland,
20892,
United States
More Information
Detailed Web Page
Publications
Liotta LA, Kleinerman J, Saidel GM. Quantitative relationships of intravascular tumor cells, tumor vessels, and pulmonary
metastases following tumor implantation. Cancer Res. 1974 May;34(5):997-1004. No abstract available.
Schumacher G, Kataoka M, Roth JA, Mukhopadhyay T. Potent antitumor activity of 2-methoxyestradiol in human pancreatic cancer
cell lines. Clin Cancer Res. 1999 Mar;5(3):493-9.
Reiser F, Way D, Bernas M, Witte M, Witte C. Inhibition of normal and experimental angiotumor endothelial cell proliferation
and cell cycle progression by 2-methoxyestradiol. Proc Soc Exp Biol Med. 1998 Dec;219(3):211-6.
Study ID Numbers:
010256; 01-C-0256
Record last reviewed:
September 1, 2004
Last Updated:
September 1, 2004
Record first received:
September 23, 2001
ClinicalTrials.gov Identifier:
NCT00024609Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-10-29