Study of IDO Inhibitor in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Metastatic Pancreatic Cancer

Inclusion Criteria:

• Patient has definitive histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas. The definitive diagnosis of metastatic pancreatic adenocarcinoma will be made by integrating the histopathological data within the context of the clinical and radiographic data. Patients with islet cell or neuroendocrine neoplasms are excluded.
• Initial diagnosis of metastatic disease must have occurred ≤8 weeks prior to entry in the study.
• Patient has one or more metastatic tumors measurable per RECIST 1.1 by CT scan ≤4 weeks prior to entry into the study (or MRI, if patient is allergic to CT contrast media). Patients cannot have nodal metastases alone even if such nodal metastases are formally considered M1 disease
• Life expectancy of greater than 3 months.
• Male or non-pregnant and non-lactating female, and ≥18 years of age.
• If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test (β-hCG) documented within 7 days prior to the first administration of study drug.
• The effects of indoximod on the developing human fetus are unknown. For this reason and because indoximod may affect maternal immune tolerance of the fetus, sexually active women of child-bearing potential must agree to use two forms of contraception (hormonal and barrier method of birth control or abstinence) prior to study entry and for the duration of study participation. Use of contraception or abstinence should continue for a minimum of 1 month after completion of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should discontinue the study drug and inform her treating physician immediately. Also men should be discouraged from fathering children while on treatment.
• Patients must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.
• Prior treatment with gemcitabine and/or nab-paclitaxel in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering toxicities are present.
• Patients cannot have received any other immunomodulatory therapies (including vaccines) as treatment for this or any other cancer.
• Patient has adequate biological parameters as demonstrated by the following blood counts at Baseline (obtained ≤14 days prior to treatment initiation):
• Absolute neutrophil count (ANC) ≥1.5 × 10^9/L
• Platelet count ≥75,000/mm3 (75 × 10^9/L)
• Hemoglobin (Hgb) ≥9 g/dL.
• Patient has the following blood chemistry levels at Baseline (obtained ≤14 days prior to randomization):
• AST (SGOT), ALT (SGPT) ≤2.5 × upper limit of normal range (ULN), unless liver metastases are clearly present, then ≤5 × ULN is allowed
• Total bilirubin ≤ULN, patients with known Gilbert's syndrome allowed up to 3x ULN.
• Serum creatinine within normal limits or calculated clearance ≥60 mL/min/1.73 m^2 for patients with serum creatinine levels above or below the institutional normal value
• Patient has acceptable coagulation studies (obtained ≤14 days prior to randomization) as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits (±15%). If the patient is on coumadin we suggest switching the patient to a low molecular weight heparin product including enoxaparin (Lovenox) and fondiparinux (Arixtra), but if not feasible then INR must be ≤ 3.
• Patient has no clinically significant abnormalities in urinalysis results (obtained ≤14 days prior to randomization).
• Patient has a Karnofsky performance status (KPS) ≥ 70.
• Patients should be asymptomatic for jaundice prior to Day 1.
• Significant or symptomatic amounts of ascites should be drained prior to enrollment.
• Pain symptoms should be stable and should not require modifications in analgesic management prior to enrollment.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Patients may not be receiving (or received prior to enrollment) any other investigational agents for metastatic disease.
• Patient has known brain metastases,
• Patient has only locally advanced disease.
• Lymph node only metastases even if considered M1 disease by official staging criteria.
• History of malignancy in the last 3 years. Patients with prior history of in situ cancer or basal or squamous cell skin cancer are eligible. Patients with other malignancies are eligible if they were cured by surgery alone or surgery plus radiotherapy and have been continuously disease-free for at least 3 years.
• Patient has active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
• Patient has known historical or active infection with HIV, hepatitis B, or hepatitis C.
• Patients with any active autoimmune disease (i.e. psoriasis, extensive atopic dermatitis, asthma, IBD, 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.
• Patient has undergone major surgery, other than diagnostic surgery (ie, surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
• Patient has a history of allergy or hypersensitivity to any of the study drugs or any of their excipients.
• Uncontrolled intercurrent illness including, but not limited to, 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, breastfeeding should be discontinued.