1-Methyl-D-Tryptophan in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery
Summary
RATIONALE: Biological therapies, such as 1-methyl-D-tryptophan, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by stimulating the immune system.
PURPOSE: This phase I trial is studying the side effects and best dose of 1-methyl-D-tryptophan in treating patients with metastatic or refractory solid tumors that cannot be removed by surgery.
Description
OBJECTIVES:
Primary
- To assess the toxicity, safety, and pharmacokinetics of escalating doses of 1-methyl-d-tryptophan (1-MT), a competitive inhibitor of the enzyme indoleamine 2,3-dioxygenase (IDO), in patients with advanced malignancies.
- To establish a maximally tolerated dose (MTD) or maximally biological effective dose (MBED) of 1-MT for future phase II and III trials.
Secondary
- To assess the ratio of kynurenine to tryptophan in patient blood samples as a means of assessing the effect of 1MT on in vivo IDO activity.
- To ascertain the ability of 1-MT to decrease the number of T-regulatory cells thereby allowing the immune system to target tumor antigens more effectively.
- To analyze the IDO expression of different tumor types through IDO immunohistochemical staining of paraffin-preserved specimens.
- To perform high performance liquid chromatography on patient urine samples to assess how 1-MT is cleared renally.
OUTLINE: This is a multicenter study.
Patients receive oral 1-methyl-d-tryptophan (1-MT) once or twice daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Blood and urine samples are assessed to characterize the pharmacokinetics of 1-MT and renal clearance rate by high performance liquid chromatography, measure tryptophan and kynurenine levels by functional assays, and measure the response of regulatory CD4+ CD25+ T cells by intracellular staining and flow cytometry. Paraffin-embedded tissue samples are analyzed for indoleamine 2,3-dioxygenase (IDO) expression by immunohistochemical staining.
After completion of study treatment, patients are followed up for 4 weeks.
Study Design
Primary Purpose: Treatment
Conditions
Unspecified Adult Solid Tumor, Protocol Specific
Intervention
1-methyl-d-tryptophan, flow cytometry, high performance liquid chromatography, immunohistochemistry staining method, laboratory biomarker analysis, pharmacological study
Location
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa
Florida
United States
33612-9497
Status
Recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00567931
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Chromatography, High Pressure Liquid
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
Chromatography, Gas
Fractionation of a vaporized sample as a consequence of partition between a mobile gaseous phase and a stationary phase held in a column. Two types are gas-solid chromatography, where the fixed phase is a solid, and gas-liquid, in which the stationary phase is a nonvolatile liquid supported on an inert solid matrix.
Countercurrent Distribution
A method of separation of two or more substances by repeated distribution between two immiscible liquid phases that move past each other in opposite directions. It is a form of liquid-liquid chromatography. (Stedman, 25th ed)
Chromatography, Liquid
Chromatographic techniques in which the mobile phase is a liquid.
Chromatography, Supercritical Fluid
A CHROMATOGRAPHY method using supercritical fluid, usually carbon dioxide under very high pressure (around 73 atmospheres or 1070 psi at room temperature) as the mobile phase. Other solvents are sometimes added as modifiers. This is used both for analytical (SFC) and extraction (SFE) purposes.
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