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

NCT ID: NCT01560923

Last Updated: 2020-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-01
• Study Completion Date: 2018-12-12

Brief 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.

Detailed 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.

Conditions

Metastatic Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Sipuleucel-T + Oral Indoximod

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.

Group Type: EXPERIMENTAL

Indoximod

Intervention Type: BIOLOGICAL

Given twice daily (1200 mg total) by mouth for 6 months.

Sipuleucel-T

Intervention Type: BIOLOGICAL

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).

Sipuleucel-T + Placebo

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

Group Type: PLACEBO_COMPARATOR

Sipuleucel-T

Intervention Type: BIOLOGICAL

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).

Placebo

Intervention Type: OTHER

Given in same manner as Indoximod; 1200 mg per day by mouth.

Interventions

Indoximod

Given twice daily (1200 mg total) by mouth for 6 months.

Intervention Type: BIOLOGICAL

Sipuleucel-T

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).

Intervention Type: BIOLOGICAL

Placebo

Given in same manner as Indoximod; 1200 mg per day by mouth.

Intervention Type: OTHER

Other Intervention Names

1-methyl-D-tryptophan; Provenge

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shilpa Gupta, M.D.

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

University of Illinois Medical Center

Chicago, Illinois, United States

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

New York Presbyterian/Weill Cornell Medical Center

New York, New York, United States

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2011LS109

Identifier Type: -

Identifier Source: org_study_id