Clinical trial NCT00028821: 2-Methoxyestradiol in Treating Patients With Advanced Solid Tumors
Official title: A Phase I and Pharmacologic Study of 2-Methoxyestradiol in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Refractory Multiple Myeloma
Stage III Multiple Myeloma
Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Maximum-tolerated dose (MTD) based on the incidence of dose-limiting toxicity (DLT) as assessed by Common Toxicity Criteria (CTC) version 2.0
timeFrame: 28 days
measure: Number of toxicity incidents as assessed by CTC version 2.0
timeFrame: Up to 3 months after completion of treatment
Secondary outcomes:
measure: Biologic activity rate (BAR)
timeFrame: At day 1 and at day 28
measure: Angiogenesis inhibition via an ex vivo angiogenesis assay
timeFrame: At day 1 and at day 28
measure: Number of responses
timeFrame: Up to 3 months after completion of treatment
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Charles Erlichman
role: PRINCIPAL_INVESTIGATOR
References: