Phase II Study of Sipuleucel-T and Indoximod for Patients With Refractory Metastatic Prostate Cancer
Condition: Metastatic Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Indoximod; Sipuleucel-T; Placebo
Intervention description: Given twice daily (1200 mg total) by mouth for 6 months.; Sipuleucel-T will be administered as standard of care. Given by infusion over 60 minutes at Week 0, 2 and 4. Patients will undergo leukapheresis at weeks 0, 2, and 4 with sipuleucel-T infused 3 days later (i.e. Monday/Thursday; Tuesday/Friday).; Given in same manner as Indoximod; 1200 mg per day by mouth.
Intervention MeSH terms: Tryptophan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 47.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hormone refractory prostate cancer

Summary:

      This is a randomized, double blind, multi-institutional phase II therapeutic study of
      Indoximod or placebo after the completion of standard of care sipuleucel-T (Provenge®) in men
      with asymptomatic or minimally symptomatic metastatic prostate cancer that is castration
      resistant (hormone refractory). Patients are randomized to receive either twice daily oral
      Indoximod or placebo for 6 months beginning the day after the third and final sipuleucel-T
      infusion.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically documented adenocarcinoma of the prostate with metastatic disease as
             evidenced by soft tissue and/or bony metastases on baseline computed tomography (CT)
             scan of the abdomen and pelvis and/or bone scan

          -  Castration-resistant based on a current or historical evidence of disease progression
             despite surgical or medical castration as demonstrated by one or more of the
             following:

               -  PSA progression (defined as two consecutive prostate specific antigen (PSA)
                  measurements at least 14 days apart ≥ 2.0 ng/ml and ≥ 50% above the minimum PSA
                  during castration therapy or above pre-treatment value if no response)

               -  progression of measurable disease based on Response Evaluation Criteria In Solid
                  Tumors (RECIST) criteria (≥ 50% increase in the sum of the cross products of all
                  measurable lesions or the development of any new lesions

               -  progression of non-measureable disease

          -  Serum PSA ≥ 2.0 ng/ml at study enrollment

          -  Castration levels of testosterone defined as ≤ 30 ng/dL at study enrollment. Must be
             at least 3 months from surgical castration or must have received medical castration
             therapy for at least 3 months and be receiving such therapy at the time of confirmed
             disease progression

          -  Asymptomatic or minimally symptomatic disease as demonstrated by Eastern Cooperative
             Oncology Group (ECOG) Performance Status 0 or 1 and no need for opiate pain
             medications to control pain/symptoms

          -  Age 18 years and old

          -  Adequate bone marrow, renal and hepatic function within 14 days of study enrollment
             defined as:

               -  Bone marrow: WBC > 3,000/uL; absolute neutrophil count > 1,500/uL; platelets >
                  100,000/uL

               -  Renal: creatinine within institutional upper limit of normal (ULN) OR creatinine
                  clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above ULN

               -  Hepatic: total bilirubin < 1.5 X institutional ULN; aspartate aminotransferase
                  (AST ((SGOT)) and alanine aminotransferase (ALT((SGPT)) < 2.5 X institutional ULN

        Exclusion Criteria:

          -  Chronic steroid dependence (should stop all steroid supplementation 4 weeks prior to
             enrollment)

          -  Human immunodeficiency virus (HIV)-positive patients and those with other
             acquired/inherited immunodeficiency

          -  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

          -  Inability to take medications by mouth

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition

          -  Active autoimmune disease, chronic inflammatory condition, conditions requiring
             concurrent use of any systemic immunosuppressants or steroids. Mild-intermittent
             asthma requiring only occasional beta-agonist inhaler use or mild localized eczema
             will not be excluded.

          -  Previous allo-transplant of any kind

          -  History of prior treatment with anti-CTLA4 blocking antibody