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Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00567931

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

A Phase 1 study testing 1-methyl-d-tryptophan, pharmacological study and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
1-methyl-d-tryptophan, pharmacological study and laboratory biomarker analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
2 sitesUnited States
Study dates
Oct 2007to Sep 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 50Show fewer
  • 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
  • Tropical sprue
  • Bacterial overgrowth/blind-loop syndrome
  • Strictures
  • Adhesions
  • Achalasia
  • Bowel obstruction
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective double-method contraception during and for at least 1 month after completion of study treatment
  • No history of allergic reactions (significant urticaria, angioedema, anaphylaxis) attributed to compounds of similar chemical or biologic composition to 1-methyl-d-tryptophan (including L-tryptophan or 5-hydroxy-tryptophan supplements)
  • No active autoimmune disease (i.e., psoriasis, extensive atopic dermatitis, asthma, inflammatory bowel disorder, multiple sclerosis, uveitis, vasculitis), chronic inflammatory condition, or any condition requiring concurrent use of any systemic immunosuppressants or steroids for any reason
  • Mild-intermittent asthma requiring only occasional beta-agonist inhaler use or mild localized eczema allowed
  • No uncontrolled concurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Myocardial infarction or percutaneous coronary interventions within the past 6 months
  • Cardiac arrhythmia
  • Active autoimmune diseases
  • Major psychiatric illness or social situation that would limit compliance with study requirements as judged by the primary investigator at each site
  • Patients with well-controlled, chronic medical conditions under the supervision of the patient's primary physician (i.e., hypertension, hyperlipidemia, coronary heart disease, diabetes mellitus) are eligible
  • No HIV-positive patients or patients with other acquired/inherited immunodeficiencies
  • No other active malignancy
  • No concurrent immunosuppressants, including steroids
  • Recovered from all prior therapy
  • No prior gastric bypass surgery
  • No prior extensive small bowel resection
  • No prior experimental active immunotherapy consisting of targeted monoclonal antibodies or pharmaceutical compounds
  • Commercially available active immunotherapy (e.g., adjuvant interferon) must have completed therapy over 1 year prior to enrollment and have no evidence of autoimmune sequelae
  • Prior therapy with approved monoclonal antibodies (e.g., bevacizumab, cetuximab, panitumumab, or trastuzumab) allowed
  • At least 4 weeks since prior and no other concurrent investigational agents
  • More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C)
  • No concurrent supplements containing L-tryptophan or derivatives
  • No patients with an allo-transplant of any kind (including those with a xenograft heart valve)
  • No other concurrent commercial agents or therapies

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
1-methyl-d-tryptophan, pharmacological study, laboratory biomarker analysis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 1-methyl-d-tryptophanDrug

    Also called indoximod

    Given orally

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00567931
Study groupRoleWhat they receive
Treatment (Immunomodulating therapy)ExperimentalPatients 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.
Receives: Drug: 1-methyl-d-tryptophan; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 4 weeks

  2. 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.

    Measured: Up to 4 weeks

Secondary outcomes (4)

  1. Pharmacokinetics of 1-methy-D-tryptophan

    Analyses of secondary endpoints will mainly be of exploratory nature. If needed, non-parametric methods such as the signed rank test and/or Spearman correlation coefficient will be considered to explore preliminarily the treatment effect on the secondary endpoints and its relationships with various potential biomarkers and therapeutic targets.

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

  2. Change in the tryptophan kynurenine ratio

    Descriptive statistics such as means, medians, interquartiles, and standard deviations (SDs) or frequencies and percentages will be reported. When appropriate, confidence intervals also will be included. Change data contrasting post-treatment vs baseline will be summarized similarly. If needed, non-parametric methods such as the signed rank test and/or Spearman correlation coefficient will be considered to explore preliminarily the treatment effect on the secondary endpoints and its relationships with various potential biomarkers and therapeutic targets.

    Measured: Baseline to up to week 5

  3. Change in the number of circulating CD4+ CD25+ Treg cells

    Descriptive statistics such as means, medians, interquartiles, and SDs or frequencies and percentages will be reported. When appropriate, confidence intervals also will be included. Change data contrasting post-treatment vs baseline will be summarized similarly. If needed, non-parametric methods such as the signed rank test and/or Spearman correlation coefficient will be considered to explore preliminarily the treatment effect on the secondary endpoints and its relationships with various potential biomarkers and therapeutic targets.

    Measured: Baseline to up to 4 weeks after completion of study treatment

  4. IDO expression in tumor tissue

    Descriptive statistics such as means, medians, interquartiles, and SDs or frequencies and percentages will be reported. When appropriate, confidence intervals also will be included. Change data contrasting post-treatment vs baseline will be summarized similarly. If needed, non-parametric methods such as the signed rank test and/or Spearman correlation coefficient will be considered to explore preliminarily the treatment effect on the secondary endpoints and its relationships with various potential biomarkers and therapeutic targets.

    Measured: At baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Dec 2007 (estimated)
  2. Study startOct 2007
  3. Primary completionJul 2012
  4. Study completionSep 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00567931
Sponsor's protocol ID
NCI-2009-00268
Other IDs
NCI-2009-00268, MCC-FL065, CDR0000576700, MCC 15267, 8045, N01CM00100, P30CA076292
Status last verified
Jul 2014
First submitted
4 Dec 2007
Last updated
24 Jul 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 1-methyl-d-tryptophan, pharmacological study and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 50 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events, graded according to the standard Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (time frame: Up to 4 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00567931.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2014.

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