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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01560923
First received: March 20, 2012
Last updated: July 8, 2014
Last verified: July 2014

March 20, 2012
July 8, 2014
October 2012
July 2015   (final data collection date for primary outcome measure)
Immune Response to Sipuleucel-T [ Time Frame: 14 Weeks from First Leukapheresis ] [ Designated as safety issue: No ]
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.
Immune Response to Sipuleucel-T [ Time Frame: 14 Weeks from First Leukapheresis ] [ Designated as safety issue: No ]
Assess the augmentation of immune response to sipuleucel-T measured at 14 weeks from first leukapheresis, in response to twice daily oral 1-MT at a dose of 1200 mg/day or an identical looking placebo
Complete list of historical versions of study NCT01560923 on ClinicalTrials.gov Archive Site
  • Time to Disease Progression [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    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.
  • Objective Response Rate [ Time Frame: 6 Months, 1 Year ] [ Designated as safety issue: No ]
    rate as defined by Prostate Cancer Working Group -2 (PCWG2)(6)
  • Overall Survival [ Time Frame: From Time of Randomization to Death ] [ Designated as safety issue: No ]
    Survival in months from time of randomization (enrollment) to death.
  • Quality of Life Scale Results [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    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
Same as current
Not Provided
Not Provided
 
Phase II Study of Sipuleucel-T and Indoximod for Patients With Refractory Metastatic Prostate Cancer
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

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Metastatic Prostate Cancer
  • 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
  • Other: Placebo
    Given in same manner as Indoximod; 1200 mg per day by mouth.
  • 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.
    Interventions:
    • Biological: Indoximod
    • Biological: Sipuleucel-T
  • Placebo Comparator: Control (Placebo) Arm
    Placebo is identical-looking to Indoximod and provided in the same manner.
    Interventions:
    • Biological: Sipuleucel-T
    • Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
July 2015
July 2015   (final data collection date for primary outcome measure)

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
Male
18 Years and older
No
Contact: Judith Witte, RN 612-626-0169 mirab001@umn.edu
United States
 
NCT01560923
2011LS109
Yes
Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
Not Provided
Principal Investigator: Gautam Jha, M.D. Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP