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

NCT00567931 | Completed Phase 1

• 7 other identifiers: NCI-2009-00268MCC-FL065CDR0000576700MCC 152678045N01CM00100P30CA076292
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events, graded according to the standard Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  All patients who receive any amount of the study drug will be evaluable for toxicity.

  Up to 4 weeks

• MTD or MBED of 1-Methyl-D-tryptophan

  A dose limiting toxicity (DLT) will be defined as any adverse events (AEs) occurring during any course when considered possibly, probably, or definitely related to therapy that is part of this study. Unacceptable AEs including any grade 3 or greater toxicity possibly, probably, or definitely due to the study drug (except oral intolerance). The MBED will be determined retrospectively after all data has been collected and an MTD has been determined.

  Up to 4 weeks

Secondary Outcomes (4)

• Pharmacokinetics of 1-methy-D-tryptophan

  At 0, 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 hours after administration

• Change in the tryptophan kynurenine ratio

  Baseline to up to week 5

• Change in the number of circulating CD4+ CD25+ Treg cells

  Baseline to up to 4 weeks after completion of study treatment

• IDO expression in tumor tissue

  At baseline

Study Arms (1)

Treatment (Immunomodulating therapy)

EXPERIMENTAL

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.

Drug: 1-methyl-d-tryptophan; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

1-methyl-d-tryptophan DRUG

Given orally

Also known as: indoximod

Treatment (Immunomodulating therapy)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (Immunomodulating therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (Immunomodulating therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed solid malignancy that is metastatic or unresectable and for which standard effective antineoplastic therapy does not exist or is no longer effective
• Patients are eligible for enrollment into the trial regardless of the types of previous therapies administered
• Patients with known brain metastases will only be eligible after their tumors have been treated with definitive resection and/or radiotherapy and they are neurologically stable for at least 1 month off steroids
• No known untreated brain metastases
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy \> 4 months
• WBC ≥ 3,000/μL
• ANC ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• No history of gastrointestinal disease causing malabsorption or obstruction, including, but not limited to, any of the following:
• Crohn's disease
• Celiac sprue

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Interventions

1-methyltryptophan

Study Officials

• Scott Antonia

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2007
• First Posted: December 5, 2007
• Study Start: October 1, 2007
• Primary Completion: July 1, 2012
• Study Completion: September 1, 2012
• Last Updated: July 24, 2014

Record last verified: 2014-07

Locations

US (2)