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A Phase I Study of 1-methyl-D-tryptophan (D-1MT) in Patients With Relapsed or Refractory Solid Tumors

Phase 1
18 Years
Not Enrolling
Breast Cancer, Lung Cancer, Melanoma, Pancreatic Cancer, Solid Tumors

Thank you

Trial Information

A Phase I Study of 1-methyl-D-tryptophan (D-1MT) in Patients With Relapsed or Refractory Solid Tumors

This protocol provides an early evaluation of an entirely new class of small molecule agents
directed at disruption or elimination of tumor tolerance, a phenomenon now demonstrated to
be involved in the growth of many solid tumors. D-1MT, or any other substance targeting this
enzymatic pathway indoleamine-(2,3)-dioxygenase (IDO), has not been used previously in
humans. Although pre-clinical toxicology in rats and dogs shows an extremely encouraging
toxicity profile, the study needs to carefully evaluate the toxicities and pharmacokinetics
to provide the basis for assigning a safe and biologically effective dosing regimen for
later trials determining its contribution to tumor responses in phase II and III clinical

Inclusion Criteria:

- A histological or cytological diagnosis of recurrent or refractory solid tumor
malignancy. The patient's pathology must be reviewed and confirmed prior to
enrollment (outside reviews acceptable). If no standard therapy exists for disease
or subject refused standard therapy, subject would be considered eligible for

- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

- Hemoglobin ≥ 9.0 gm/dL, absolute neutrophil count (ANC) ≥1200/mm3, platelets
≥100,000/mm3, absolute lymphocyte count ≥800/mm3.

- Hepatic: serum total bilirubin ≤ 1.5 x ULN mg/dL, ALT (SGPT) and AST (SGOT) ≤2.5 x
upper limit of normal (ULN).

- Renal: serum creatinine (sCr) ≤1.5 x ULN, or creatinine clearance (Ccr) ≥50 mL/min
(approximation by Cockcroft and Gault accepted)

- Life expectancy of greater than 4 months.

- Measurable or non-measurable disease

- Normal EKG including benign variants or abnormalities associated with any condition
currently responding to appropriate care (e.g., controlled hypertension with minimal
or moderate LVH, controlled AF).

- Prior therapy may include any number of chemotherapy, immunotherapy, and/or radiation
therapy regimens. Major surgery or systemic chemotherapy must have been completed at
least 4 weeks prior to enrollment and residual toxicities from that therapy must be
Grade 1 or lower at the time of enrollment with the exception of hemoglobin and
absolute granulocyte count. Localized radiation therapy must have been completed at
least 2 weeks prior to enrollment and residual toxicities must be Grade 1 or lower at
the time of enrollment.

- Patients must have the ability to understand the study, its inherent risks, side
effects and potential benefits and be able to give written informed consent to

- Male and female subjects of child producing potential must agree to use contraception
or avoidance of pregnancy measures while enrolled on study and receiving the
experimental drug, and for one month after the last dose of drug.

- Patients must be at least 18 years of age

Exclusion Criteria:

- Active CNS metastases or carcinomatous meningitis. Patients with CNS metastases must
be at least 3 months status post of prior therapy to the brain and be off all
steroids without progressing CNS disease.

- Pregnant or nursing women due to the unknown effects of study drug on the developing
fetus or newborn infant.

- 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.

- History of organ transplant.

- Subjects with autoimmune disease, either active or by history (e.g., systemic lupus
erythematosis (SLE), rheumatoid arthritis (RA), scleroderma, dermatomyositis, etc.).

- Subjects receiving immunosuppressive therapy including systemic corticosteroid
therapy and/other immunosuppressive therapy (methotrexate, cyclosporine, FK-506,
rapamycin) for any reason. Subjects receiving inhaled or topical corticosteroids are

- Significant or uncontrolled cardiovascular disease to include: uncontrolled
hypertension (blood pressure must be ≤ 150/90 mmHg at the time of enrollment on a
stable antihypertensive regimen); New York Heart Association grade II or greater
congestive heart failure (CHF); grade II or greater peripheral vascular disease;
significant ventricular arrhythmias requiring medication; and myocardial infarction
or unstable angina < six months prior to enrollment.

- Active uncontrolled infection requiring antibiotics within 1-week prior to study,
including unexplained fever (temp > 38.1°C or >100.6°F).

- Any condition, psychiatric or otherwise, that would preclude informed consent,
consistent follow-up or compliance with any aspect of the study (e.g., untreated
schizophrenia or other significant cognitive impairment, etc.).

- No supplements containing L-trytophan or derivatives thereof are allowed to be taken
while on study.

- Patients with positive serology for HIV, Hepatitis B or C, and patients with other
acquired/inherited immunodeficiencies are ineligible due to the possibility of
affecting the response to D-1MT and the higher risk of active opportunistic

- Patients with more than one active malignancy at the time of enrollment.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the safety and efficacy of administration of D-1MT into patients with recurrent or refractory solid tumors. Establish the toxicities of D-1MT and define any dose limiting toxicities if they occur below the maximum doses.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Charles J. Link, M.D.

Investigator Role:

Study Chair

Investigator Affiliation:

NewLink Genetics Corporation


United States: Food and Drug Administration

Study ID:




Start Date:

August 2008

Completion Date:

October 2012

Related Keywords:

  • Breast Cancer
  • Lung Cancer
  • Melanoma
  • Pancreatic Cancer
  • Solid Tumors
  • Breast Neoplasms
  • Lung Neoplasms
  • Melanoma
  • Pancreatic Neoplasms
  • Neoplasms



Vanderbilt University Nashville, Tennessee  37232-6305