A Phase II Double-Blinded, Randomized, Placebo-Controlled Study of Docetaxel in Combination With 1-methyl-D-tryptophan (Indoximod) in Metastatic Breast Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed estrogen/progesterone receptors (ER/PR)
+/-; human epidermal growth factor receptor 2 (HER2)-, metastatic breast cancer.

- Measureable disease, defined as at least one lesion that can be accurately measured
in at least one dimension (longest diameter to be recorded for non-nodal lesions and
short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm
with spiral CT scan, MRI, or calipers by clinical exam.

- Any number of prior endocrine therapies in the metastatic setting are allowed. The
patient must not have received any prior chemotherapy agents in the metastatic
setting. Prior treatment with adjuvant docetaxel is allowed if disease relapse
occurred greater than 12 months from the completion of adjuvant therapy.

- Age ≥18 years.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (Karnofsky ≥60%).

- Life expectancy of greater than 4 months.

- Patients must have normal organ and marrow function as defined below: leukocytes
≥3,000/mcL, absolute neutrophil count ≥1,500/mcL, platelets ≥100,000/mcL, total
bilirubin within normal institutional limits, aspartate aminotransferase AST(SGOT)/
alanine aminotransferase ALT(SGPT) ≤2.5 X institutional upper limit of normal,
creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73
m^2 for patients with creatinine levels above institutional normal.

- 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.

- Male and female subjects of child producing potential must agree to use adequate
forms of contraception or avoidance of pregnancy measures prior to study entry, while
enrolled on study and for a minimum of one month after completion of the study.

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

Exclusion Criteria:

- Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 3 weeks earlier.

- Patients who are currently receiving any other investigational agents.

- Patients with known active, untreated brain metastases should be excluded from this
clinical trial. Those with previously treated inactive brain metastases with no
evidence of active disease documented on brain MRI at least 4 weeks after radiation
and off all steroids may be eligible.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to docetaxel or tryptophan containing substances. This would include
L-tryptophan or 5-hydroxy-tryptophan supplements. Also patients with a history of
severe hypersensitivity reactions to docetaxel or to other drugs formulated with
polysorbate 80 are excluded.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Pregnant women are excluded from this study because 1-Methyl-D-tryptophan is an
immunoregulatory agent with the potential for abortifacient effects due to fetal
rejection by the maternal immune system. Because there is an unknown but potential
risk for adverse events in nursing infants secondary to treatment of the mother with
1-Methyl-D-tryptophan, breastfeeding should be discontinued if the mother is treated
with 1-Methyl-D-tryptophan. Also, docetaxel is a category D cytotoxic agent and is
not administered to pregnant females.

- Known HIV-positive patients and those with other acquired/inherited
immunodeficiencies are ineligible due to the possibility of affecting the response to
indoximod and the higher risk of active opportunistic infections.

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

- Patients who have received any prior experimental active immunotherapy consisting of
targeted monoclonal antibodies (ipilimumab) or pharmaceutical compounds are excluded.

- Patients with any active autoimmune disease (i.e. psoriasis, extensive atopic
dermatitis, asthma, inflammatory bowel disease (IBD), multiple sclerosis (M.S.),
uveitis, vasculitis), chronic inflammatory condition, or any condition requiring
concurrent use of any systemic immunosuppressants or steroids for any reason would be
excluded from the study. Any patient with an allo-transplant of any kind would be
excluded as well. This would include those with a xenograft heart valve to avoid the
potential risk of any immune reaction causing valvular degeneration.
Mild-intermittent asthma requiring only occasional beta-agonist inhaler use or mild
localized eczema will not be excluded.