1-Methyl-D-Tryptophan in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery
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.
- 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.
- 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.
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
1-methyl-d-tryptophan, flow cytometry, high performance liquid chromatography, immunohistochemistry staining method, laboratory biomarker analysis, pharmacological study
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
National Cancer Institute (NCI)
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00567931
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.
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.
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)
Chromatographic techniques in which the mobile phase is a liquid.
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.
The purpose of this study is twofold. The first objective is to find the highest dose of 1-Methyl-D-tryptophan (shortened to 1-MT) combined with a vaccine called Ad.p53 DC that can be giv...
The purpose of this study is to: - see if 1-Methyl-D-tryptophan is safe - collect information on how the patient's body responds to this study drug - find the highest dos...
RATIONALE: White button mushroom extract may stop or delay the recurrence of breast cancer in postmenopausal breast cancer survivors. PURPOSE: This phase I trial is studying the side effe...
RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about the affect of body mass index on the way anticancer drugs work in the bod...
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth...
ObjectiveTo investigate which one, 1-methyl-L-tryptophan (1-L-MT) or 1-methyl-D-tryptophan (1-D-MT), induces immune imbalance at maternal-fetal interface in mice. Methods BALB/c female mice are mated...
We evaluated high-performance liquid chromatography (HPLC) for species identification of mycobacteria from various clinical specimens in an urban hospital in South Korea between January 2005 and Decem...
To establish a method for determining cyanamide in workplace air by high-performance liquid chromatography (HPLC).
A simple high-performance liquid chromatography method for the determination of cefovecin in small volume plasma has been developed. Following solid-phase extraction using Oasis HLB cartridges, sample...
Determination of congo red in beef by high performance liquid chromatography-tandem quadrupole time of flight mass spectrometry and ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry.
A method was developed for the determination of congo red in beef. The analyte was identified by high performance liquid chromatography-tandem quadrupole time of flight mass spectrometry (LC-QTOF MS)...