phase ii study of sipuleucel-t and indoximod for patients with refractory metastatic prostate cancer

Conditions: Metastatic 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.

sipuleucel-t will be administered as standard of care. oral indoximod/placebo will be self-administered twice daily for 6 months starting after the last infusion of sipuleucel-t. patients will be treated for a minimum of 12 weeks of indoximod/placebo before disease progression can be declared and indoximod/placebo will not be discontinued for increasing prostate specific antigen (psa) in the absence of symptomatic clinical progression.

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

Keywords: hormone refractory prostate cancer