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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01560923
Recruitment Status : Active, not recruiting
First Posted : March 22, 2012
Last Update Posted : September 26, 2018
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

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.

Condition or disease Intervention/treatment Phase
Metastatic Prostate Cancer Biological: Indoximod Biological: Sipuleucel-T Other: Placebo Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Phase II Study of Sipuleucel-T (Provenge®) Followed by Indoximod or Placebo in the Treatment of Patients With Asymptomatic or Minimally Symptomatic Metastatic Castration Resistant Prostate Cancer
Actual Study Start Date : October 1, 2012
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Treatment Arm
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.
Biological: Indoximod
Given twice daily (1200 mg total) by mouth for 6 months.
Other Name: 1-methyl-D-tryptophan

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).
Other Name: Provenge

Placebo Comparator: Control (Placebo) Arm
Placebo is identical-looking to Indoximod and provided in the same manner.
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).
Other Name: Provenge

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

Primary Outcome Measures :
  1. Immune Response to Sipuleucel-T [ Time Frame: 14 Weeks from First Leukapheresis ]
    Assess the augmentation of immune response to sipuleucel-T measured at 14 weeks from first leukapheresis, in response to twice daily oral Indoximod at a dose of 1200 mg/day or an identical looking placebo.

Secondary Outcome Measures :
  1. Time to Disease Progression [ Time Frame: 6 Months ]
    Progression free survival (PFS) is a composite endpoint defined as disease progression in bone or soft tissues, PSA progression, worsening pain, or death. PFS will be measured in months from the time of study enrollment until the date disease progression.

  2. Objective Response Rate [ Time Frame: 6 Months, 1 Year ]
    rate as defined by Prostate Cancer Working Group -2 (PCWG2)(6)

  3. Overall Survival [ Time Frame: From Time of Randomization to Death ]
    Survival in months from time of randomization (enrollment) to death.

  4. Quality of Life Scale Results [ Time Frame: 6 Months ]
    will be measured by the FACT-P (a validated questionnaire consisting of four subscales of wellbeing: Physical, Social/Family, Emotional and Functional) and compared between treatment groups

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01560923

United States, Illinois
University of Illinois Medical Center
Chicago, Illinois, United States, 60612
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New York
New York Presbyterian/Weill Cornell Medical Center
New York, New York, United States, 10065
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Principal Investigator: Shilpa Gupta, M.D. Masonic Cancer Center, University of Minnesota

Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT01560923     History of Changes
Other Study ID Numbers: 2011LS109
First Posted: March 22, 2012    Key Record Dates
Last Update Posted: September 26, 2018
Last Verified: September 2018

Keywords provided by Masonic Cancer Center, University of Minnesota:
hormone refractory prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs