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

Phase 1
18 Years
Open (Enrolling)
Solid Tumor

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Trial Information

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

Treatment will be administered on an outpatient basis. The medication will be orally
administered twice daily an hour prior to breakfast and dinner with water. Each treatment
cycle is comprised of 28 days. The treatment is continuous with no breaks in between
cycles. For dose levels 6 & 7, no single dose pharmacokinetic (PK) analysis will be done
(as this has already been done) and patients will be monitored in the Clinical Research Unit
(CRU) for one hour following first dose. Starting with dose level 8, single dose PK will be
performed as follows. Patients will be monitored during administration of their first dose
by clinical research nursing staff while pharmacokinetics tests are performed over the
initial 12 hours. This includes documenting vital signs and clinical status in hourly
intervals for the first 4 hours after administration then every 4 hours thereafter if the
patient is stable. Any acute change in patient status will be evaluated and treated by the
research medical staff. In order to collect reliable single dose pharmacokinetic data,
patients will take their first dose of 1-MT and not take another dose until day 3 of the
first cycle. All doses will be recorded by the patient using the pill diary form and
confirmed using pill counts by the research staff at each biweekly visit. The pill diary
forms will be turned into the research staff at the end of each treatment cycle. Patients
who demonstrate radiologically confirmed progressive disease will be removed from the study.
Those with stable disease or better will be treated for up to 12 cycles. No
investigational or commercial agents or therapies other than those described below may be
administered with the intent to treat the patient's malignancy. The evaluations and tests
will be performed on the schedule outlined in the schema and study calendar sections. An
autoimmunity symptom checklist will be completed at each visit by the evaluating medical

Inclusion Criteria:

- Patients must have histologically confirmed solid malignancy that is metastatic or
unresectable and for which standard effective anti-neoplastic 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 should have recovered from the acute
toxicities associated with the most recent regimen and should have been off treatment
with investigational agents for 4 weeks (6 weeks minimum for nitrosoureas or
mitomycin C).

- Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Karnofsky ≥ 60%)

- Life expectancy > 4 months

- Normal organ and marrow function: 1eukocytes ≥3,000/mcL; absolute neutrophil count
≥1,500/mcL; platelets ≥100,000/mcL; total bilirubin ≤1.5 X institutional upper limit
of normal (ULN); aspartic transaminase (AST) [SGOT]/alanine transaminase (ALT)[SGPT]
≤2.5 X institutional ULN; creatinine within normal institutional ULN; OR, creatinine
clearance ≥60 mL/min/1.73 m² for patients with creatinine levels above ULN.

- Patients with known brain metastases will only be eligible after tumors have been
treated with definitive resection and/or radiotherapy and they are neurologically
stable for at least 1 month off steroids.

- No history of gastrointestinal disease causing malabsorption or obstruction such as
but not limited to Crohn's disease, celiac sprue, tropical sprue, bacterial
overgrowth/blind loop syndrome, gastric bypass surgery, strictures, adhesions,
achalasia, bowel obstruction, or extensive small bowel resection.

- Sexually active women of child-bearing potential must agree to use 2 forms of
acceptable contraception prior to study entry, for duration of participation, and for
a minimum of 1 month after completion of the study. Women who know or suspect that
they have become pregnant during the study, should discontinue the study drug and
inform treating physician immediately. Pregnancy test is required prior to study
enrollment and monthly while on treatment with 1-MT. Men should be discouraged from
fathering children while on treatment.

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Chemotherapy or radiotherapy treatment within 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to entering study or those who have not recovered from adverse
events due to agents administered more than 4 weeks earlier.

- May not be receiving any other investigational agents

- Patients with known untreated brain metastases are excluded. Patients with previously
treated lesions as specified in the protocol document will not be excluded.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to 1-Methyl-D-tryptophan. This would include L-tryptophan or
5-hydroxy-tryptophan supplements.

- 1-MT is not metabolized through the p450 cytochrome, so there are no specific
exclusions for such medications that are metabolized through this pathway. No
supplements containing L-tryptophan or derivatives thereof are allowed to be taken
while on study. Antacid compounds should be timed a minimum of 2 hours before or
after ingestion of 1-MT.

- Active autoimmune disease, chronic inflammatory condition, conditions requiring
concurrent use of any systemic immunosuppressants or steroids. Patients with an
allo-transplant of any kind. Mild-intermittent asthma requiring only occasional
beta-agonist inhaler use or mild localized eczema will not be excluded.

- Uncontrolled concurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, myocardial
infarction or percutaneous coronary interventions within the last 6 months, cardiac
arrhythmia, active autoimmune diseases, or major psychiatric illness/social
situations that would limit compliance with study requirements as judged by the
principal investigator (PI) at each site. Those with well controlled, chronic
medical conditions under the supervision of the patient's primary physician (i.e.
hypertension, hyperlipidemia, coronary heart disease, diabetes mellitus) would not be

- Women pregnant or breastfeeding

- Human immunodeficiency virus (HIV)-positive patients and those with other
acquired/inherited immunodeficiencies are ineligible.

- Having more than 1 active malignancy at time of enrollment

- Patients who have received any prior experimental active immunotherapy consisting of
targeted monoclonal antibodies or pharmaceutical compounds are excluded. Prior
experimental vaccine patients may be enrolled if approved by the PI. Patients who
have received commercially available active immunotherapies such as 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
such as bevacizumab, cetuximab, panitumumab, or trastuzumab are not excluded.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

The study is a phase I trial with the primary objective of establishing the MTD or maximally biological effective dose (MBED) for a future phase II trial. A 3+3 dose escalation scheme will be used.

Outcome Time Frame:

Up to 12 months

Safety Issue:


Principal Investigator

Scott Antonia, M.D., PhD.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Institutional Review Board

Study ID:




Start Date:

October 2007

Completion Date:

November 2012

Related Keywords:

  • Solid Tumor
  • IDO expression
  • active solid tumor
  • immune system
  • immunomodulatory
  • advance malignancies
  • Neoplasms



H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida  33612
VCU Massey Cancer Center Richmond, Virginia  23298