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

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
excluded.

- 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.