NCT00567931

1-Methyl-D-Tryptophan in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery

A Phase 1 Study of 1-Methyl-D-tryptophan in Patients With Advanced Malignancies

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 52 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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. 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.

Detailed description

PRIMARY OBJECTIVES: I. 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. II. To establish a maximally tolerated dose (MTD) or maximally biological effective dose (MBED) of 1-MT for future phase II and III trials. SECONDARY OBJECTIVES: I. 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. II. 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. III. To analyze the IDO expression of different tumor types through IDO immunohistochemical staining of paraffin-preserved specimens. IV. To perform high performance liquid chromatography on patient urine samples to assess how 1-MT is cleared renally. OUTLINE: This is a dose-escalation 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.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	1-methyl-d-tryptophan	Given orally
OTHER	pharmacological study	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2007-10-01
• Primary completion: 2012-07-01
• Completion: 2012-09-01
• First posted: 2007-12-05
• Last updated: 2014-07-24

Locations

2 sites across 1 country: United States