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
  Purpose

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 Intervention Phase
Metastatic Prostate Cancer
Biological: Indoximod
Biological: Sipuleucel-T
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 50
Study Start Date: October 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01560923

Contacts
Contact: Judith Witte, RN 612-626-0169 mirab001@umn.edu

Locations
United States, Illinois
University of Illinois Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Arkadiusz Z Dudek, MD, PhD    312-413-8878    adudek@uic.edu   
Principal Investigator: Arkadiusz Z Dudek, MD, PhD         
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Gautam Jha, M.D.    612-625-5373    jhaxx014@umn.edu   
Principal Investigator: Gautam Jha, M.D.         
United States, Nebraska
VA Medical Center, University of Nebraska Not yet recruiting
Omaha, Nebraska, United States, 68198
Contact: George P. Hemstreet, M.D.    402-203-2043      
Principal Investigator: George P. Hemstreet, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Gautam Jha, M.D. Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01560923     History of Changes
Other Study ID Numbers: 2011LS109
Study First Received: March 20, 2012
Last Updated: July 8, 2014
Health Authority: United States: Food and Drug Administration

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
Neoplasms
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on September 16, 2014