Phase II Study of Sipuleucel-T and Indoximod for Patients With Refractory Metastatic Prostate Cancer

University of Minnesota (UMN)

Status and phase: Completed; Phase 2

Conditions: Metastatic Prostate Cancer

Treatments: Biological: Sipuleucel-T; Other: Placebo; Biological: Indoximod

Study type: Interventional

Funder types: Other

Identifiers

NCT01560923

2011LS109

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 47 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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47 participants in 2 patient groups, including a placebo group

Sipuleucel-T + Oral Indoximod

Experimental group

Description:

Oral Indoximod will be self-administered by mouth twice daily (1200 mg) for 6 months starting after the last (3rd) infusion of sipuleucel-T. Indoximod is a sterile tan powder compounded in capsule form of 200 mg.

Treatment:

Biological: Indoximod

Biological: Sipuleucel-T

Sipuleucel-T + Placebo

Placebo Comparator group

Description:

Placebo is identical-looking to Indoximod and provided in the same manner.

Treatment:

Other: Placebo

Biological: Sipuleucel-T