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

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ClinicalTrials.gov Identifier: NCT01560923
Recruitment Status : Completed
First Posted : March 22, 2012
Results First Posted : April 3, 2020
Last Update Posted : April 3, 2020
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE March 20, 2012
First Posted Date  ICMJE March 22, 2012
Results First Submitted Date  ICMJE March 6, 2020
Results First Posted Date  ICMJE April 3, 2020
Last Update Posted Date April 3, 2020
Actual Study Start Date  ICMJE October 1, 2012
Actual Primary Completion Date December 12, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2020)
Immune Response to Sipuleucel-T [ Time Frame: 14 Weeks from First Leukapheresis ]
Assess the augmentation of immune response (PA2024) 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. The frequency of antigen specific, cytokine producing cells will be determined by an ELISPOT assay. ELISPOT assay will use whole PBMC to assess interferon gamma production in response to the immunizing protein PA2024. Increase in number of ELISPOT responses to PBMC in patients in the treatment arm will be compared to those in control arm.
Original Primary Outcome Measures  ICMJE
 (submitted: March 21, 2012)
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 1-MT at a dose of 1200 mg/day or an identical looking placebo
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2020)
  • Number of Participants With Progression Free Survival at 6 Months [ 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 of disease progression. Progression is evaluated using the international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009]. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
  • Objective Response Rate [ Time Frame: 4 weeks ]
    rate as defined by Prostate Cancer Working Group -2 (PCWG2). ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST)(version 1.1) Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesion. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
  • Overall Survival [ Time Frame: 2 years ]
    To evaluate 2 year overall survival
  • Quality of Life Scale Results [ Time Frame: 6 Months ]
    measured by the performance status with scale of 0-5 0 being 'normal activity' and 5 'being dead'
  • Ratio of Antibodies to PA2024 [ Time Frame: 14 Weeks from First Leukapheresis ]
    Assess the augmentation of immune response (PA2024) 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. The frequency of antigen specific, cytokine producing cells will be determined by an ELISPOT assay. ELISPOT assay will use whole PBMC to assess interferon gamma production in response to the immunizing protein PA2024. Antibodies to PA2024 is measured by ELISA. The ratio of antibodies to ELISPOT responses to PBMC in patients in the treatment arm will be compared to those in control arm.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2012)
  • 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.
  • Objective Response Rate [ Time Frame: 6 Months, 1 Year ]
    rate as defined by Prostate Cancer Working Group -2 (PCWG2)(6)
  • Overall Survival [ Time Frame: From Time of Randomization to Death ]
    Survival in months from time of randomization (enrollment) to death.
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Study of Sipuleucel-T and Indoximod for Patients With Refractory Metastatic Prostate Cancer
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Prostate Cancer
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Biological: Indoximod
    • Biological: Sipuleucel-T
  • Placebo Comparator: Sipuleucel-T + Placebo
    Placebo is identical-looking to Indoximod and provided in the same manner.
    Interventions:
    • Biological: Sipuleucel-T
    • Other: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 7, 2016)
47
Original Estimated Enrollment  ICMJE
 (submitted: March 21, 2012)
50
Actual Study Completion Date  ICMJE December 12, 2018
Actual Primary Completion Date December 12, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01560923
Other Study ID Numbers  ICMJE 2011LS109
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Shilpa Gupta, M.D. Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date March 2020

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