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Sipuleucel-T and Low-protein Diet in Patients With Metastatic Castrate-resistant Prostate Cancer

NCT03329742

Description:

This is a single-center, randomized, open-label study to assess the feasibility of a low-protein diet intervention in patients with metastatic castrate-resistant prostate cancer (CRPC) who are receiving treatment with sipuleucel-T. Subjects will be randomized (1:1 ratio) to either Arm 1 or Arm 2 (Fig. 1). Arm 1: Subjects randomized to Arm 1 will be treated with sipuleucel-T infusion on Day 1, every two weeks for a total of three infusions. Subjects on this arm will receive a control diet containing 20% protein. Arm 2: Subjects randomized to Arm 2 will be treated with sipuleucel-T infusion on Day 1, every two weeks for a total of three infusions. Subjects on this arm will receive a low-protein diet containing 10% protein. Patients with metastatic, asymptomatic or minimally symptomatic CRPC that has progressed despite androgen deprivation therapy will be eligible for the study. After informed consent eligible patients will be scheduled to receive sipuleucel-T (three infusions two weeks apart) with normal-protein diet vs. low-protein diet. Each cycle will be every 14 days. Diet intervention will commence 1 week prior to the first apheresis (Day -7) and will continue until 10 days after the last infusion of sipuleucel-T (Day +42) (Fig. 2).

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Sipuleucel-T and Low-protein Diet in Patients With Metastatic Castrate-resistant Prostate Cancer
  • Official Title: A Pilot Feasibility Study of Sipuleucel-T vs. Sipuleucel-T and Low-protein Diet in Patients With Metastatic Castrate-resistant Prostate Cancer (CRPC)

Clinical Trial IDs

  • ORG STUDY ID: IUSCC-0614
  • SECONDARY ID: 1706081520
  • NCT ID: NCT03329742

Conditions

  • Prostate Cancer Recurrent

Purpose

This is a single-center, randomized, open-label study to assess the feasibility of a low-protein diet intervention in patients with metastatic castrate-resistant prostate cancer (CRPC) who are receiving treatment with sipuleucel-T. Subjects will be randomized (1:1 ratio) to either Arm 1 or Arm 2 (Fig. 1). Arm 1: Subjects randomized to Arm 1 will be treated with sipuleucel-T infusion on Day 1, every two weeks for a total of three infusions. Subjects on this arm will receive a control diet containing 20% protein. Arm 2: Subjects randomized to Arm 2 will be treated with sipuleucel-T infusion on Day 1, every two weeks for a total of three infusions. Subjects on this arm will receive a low-protein diet containing 10% protein. Patients with metastatic, asymptomatic or minimally symptomatic CRPC that has progressed despite androgen deprivation therapy will be eligible for the study. After informed consent eligible patients will be scheduled to receive sipuleucel-T (three infusions two weeks apart) with normal-protein diet vs. low-protein diet. Each cycle will be every 14 days. Diet intervention will commence 1 week prior to the first apheresis (Day -7) and will continue until 10 days after the last infusion of sipuleucel-T (Day +42) (Fig. 2).

Detailed Description

      Primary Objective To assess the feasibility of low-protein diet intervention in patients with
      metastatic CRPC receiving immunotherapy with sipuleucel-T. Change in blood urea nitrogen
      (BUN) and urine urea nitrogen (UUN) from baseline to 6 weeks will be measured to assess
      adherence of following the diet intervention. The expected changes (mean, standard deviation)
      in BUN are 5.5 ± 2.6 mg/dL with 10% protein diet arm and 2.5 ± 2.6 mg/dL with 20% protein
      diet arm (please see section 12.5.7).

      Secondary Objectives

        1. To assess whether low-protein diet intervention augments the immune response to
           sipuleucel-T in men with metastatic CRPC.

        2. To assess the safety and tolerability of the combination of sipuleucel-T and low-protein
           diet intervention.

        3. To obtain preliminary evidence of clinical efficacy of the combination of sipuleucel-T
           and low-protein diet compared to sipuleucel-T and control-diet, including objective
           response rate (partial + complete response), progression-free survival (PFS) and overall
           survival (OS), and changes in prostate-specific antigen (PSA).
    

Trial Arms

NameTypeDescriptionInterventions
Control protein diet armPlacebo Comparator20% protein content
    Low protein diet armExperimental10% protein content

      Eligibility Criteria

              ELIGIBILITY CRITERIA Men at least 18 years of age with asymptomatic or minimally
              symptomatic, metastatic, androgen independent prostate cancer will be recruited for this
              study. Before the initiation of screening procedures, the patient will undergo the Informed
              Consent Process which includes signing an Institutional Review Board (IRB)-approved consent
              form. The subject will subsequently undergo screening assessments to determine if he meets
              the eligibility criteria for the study.
      
              Inclusion Criteria
      
                -  Histologically documented adenocarcinoma of the prostate.
      
                -  Metastatic disease as evidenced by soft tissue and/or bony metastases on baseline bone
                   scan and/or computed tomography (CT) scan of the chest, abdomen, and pelvis
      
                -  Androgen independent prostatic adenocarcinoma. Subjects must have current or
                   historical evidence of disease progression concomitant with surgical or medical
                   castration, as demonstrated by PSA progression OR progression of measurable disease OR
                   progression of non-measurable disease as defined below:
      
                     -  PSA: Two consecutive PSA values, at least 14 days apart, each ≥ 5.0 ng/mL and ≥
                        50% above the minimum PSA observed during castration therapy or above the
                        pre-treatment value if there was no response.
      
                     -  Measurable disease: At least a 20% increase in the sum of diameters of target
                        lesions, taking as reference the smallest sum on study (this includes the
                        baseline sum if that is the smallest on study). In addition to the relative
                        increase of 20%, the sum must also demonstrate an absolute increase of at least 5
                        mm. The change will be measured against the best response to castration therapy
                        or against the pre-castration measurements if there was no response.
      
                     -  Non-measurable disease: Soft tissue disease: The appearance of 1 or more new
                        lesions, and/or unequivocal worsening of non-measurable disease when compared to
                        imaging studies acquired during castration therapy or against the pre-castration
                        studies if there was no response.
      
                     -  Bone disease: Appearance of 2 or more new areas of abnormal uptake on bone scan
                        when compared to imaging studies acquired during castration therapy or against
                        the pre-castration studies if there was no response. Increased uptake of
                        pre-existing lesions on bone scan does not constitute progression.
      
                     -  Serum PSA ≥ 5.0 ng/mL
      
                     -  Castration levels of testosterone (< 50 ng/dL) achieved via medical or surgical
                        castration. Surgical castration must have occurred at least 3 months prior to
                        registration. Subjects who are not surgically castrate must be receiving medical
                        castration therapy, have initiated such therapy at least 3 months prior to
                        registration, and continue such therapy until the time of confirmed objective
                        disease progression.
      
                -  Life expectancy of at least 6 months
      
                -  Men ≥ 18 years of age
      
                -  Adequate hematologic, renal, and liver function as evidenced by the following:
      
                     -  White blood cell (WBC) ≥ 2,500 cells/μL
      
                     -  Absolute neutrophil count (ANC) ≥ 1,000 cells/μL
      
                     -  Platelet Count ≥ 100,000 cells/μL
      
                     -  Hemoglobin (HgB) ≥ 9.0 g/dL
      
                     -  Creatinine ≤ 2.0 mg/dL
      
                     -  Total bilirubin ≤ 2 x upper limit of normal (ULN)
      
                     -  Aspartate aminotransaminase (AST, SGOT) ≤ 2.5 x ULN
      
                     -  Alanine aminotransaminase (ALT, SGPT) ≤ 2.5 x ULN
      
              Exclusion Criteria
      
                -  The presence of lung, liver, or known brain metastases, malignant pleural effusions,
                   or malignant ascites.
      
                -  Moderate or severe symptomatic metastatic disease. Subjects who meet either of the
                   following criteria must be excluded:
      
                     -  A requirement for treatment with opioid analgesics for any reason within 28 days
                        prior to registration
      
                     -  Average weekly pain score of 4 or more as reported on the 10-point Visual Analog
                        Scale (VAS) on the Registration Pain Log
      
                -  Eastern Cooperative Oncology Group (ECOG) performance status > 2
      
                -  Use of non-steroidal antiandrogens (e.g., flutamide, nilutamide, or bicalutamide)
                   within 6 weeks of registration.
      
                -  Treatment with chemotherapy within 28 days of registration including subjects who
                   received more than 2 chemotherapy regimens in the metastatic setting at any time prior
                   to registration.
      
                -  Treatment with any of the following medications or interventions within 28 days of
                   registration:
      
                     -  Systemic corticosteroids; however, use of inhaled, intranasal, and topical
                        steroids is acceptable.
      
                     -  Ketoconazole
      
                     -  High dose calcitriol [1,25(OH)2VitD] (i.e., > 7.0 μg/week)
      
                     -  Any other systemic therapy for prostate cancer (except for medical castration)
      
                -  Prior treatment with sipuleucel-T (on clinical trial or as part of standard of care)
      
                -  Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical
                   erosion on radiography > 50%) or spinal cord compression
      
                -  Paget's disease of bone
      
                -  A history of stage III or greater cancer, excluding prostate cancer. Basal or squamous
                   cell skin cancers must have been adequately treated and the subject must be
                   disease-free at the time of registration. Subjects with a history of stage I or II
                   cancer must have been adequately treated and been disease-free for ≥ 3 years at the
                   time of registration.
      
                -  A requirement for systemic immunosuppressive therapy for any reason
      
                -  Any infection requiring parenteral antibiotic therapy or causing fever (temperature >
                   100.5°F or 38.1°C) within 1 week prior to registration
      
                -  A known allergy, intolerance, or medical contraindication to receiving the contrast
                   dye required for the protocol-specified CT imaging
      
                -  Any medical intervention or other condition which, in the opinion of the Principal
                   Investigator, could compromise adherence with study requirements or otherwise
                   compromise the study's objectives
            
      Maximum Eligible Age:N/A
      Minimum Eligible Age:18 Years
      Eligible Gender:Male
      Healthy Volunteers:No

      Primary Outcome Measures

      Measure:Adherence to diet intervention
      Time Frame:6 weeks
      Safety Issue:
      Description:BUN and UUN laboratory values

      Secondary Outcome Measures

      Measure:Feasibility of diet intervention
      Time Frame:6 weeks
      Safety Issue:
      Description:Patient self-report of compliance
      Measure:Feasibility of diet intervention
      Time Frame:6 weeks
      Safety Issue:
      Description:Rate of drop-out
      Measure:Feasibility of diet intervention
      Time Frame:6 weeks
      Safety Issue:
      Description:Rate of enrollment
      Measure:Safety and tolerability of diet intervention combined with sipuleucel-T treatment
      Time Frame:6 weeks
      Safety Issue:
      Description:Rate of adverse events per CTCAE
      Measure:Rate of immune response
      Time Frame:6, 12, and 14 weeks
      Safety Issue:
      Description:IFN-γ ELISpot specific for PA2024 laboratory values
      Measure:Progression free survival
      Time Frame:2 years
      Safety Issue:
      Description:Length of time during and after the treatment that a patient lives with the disease but it does not get worse
      Measure:Overall survival
      Time Frame:2 years
      Safety Issue:
      Description:Length of time start of treatment that patients are still alive

      Details

      Phase:N/A
      Primary Purpose:Interventional
      Overall Status:Recruiting
      Lead Sponsor:Indiana University

      Last Updated