Concurrent vs. Sequential Sipuleucel-T & Abiraterone Treatment in Men With Metastatic Castrate Resistant Prostate Cancer
Condition: Prostate Cancer Metastatic; Hormone Refractory Prostate Cancer; Castration-resistant Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: sipuleucel-T; abiraterone acetate
Intervention description: Sipuleucel-T is an autologous cell product consisting of antigen presenting cells (APCs) loaded with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).; Abiraterone acetate (1000 mg po QD) was administered in combination with prednisone (5 mg po BID) for a total of 26 weeks.
Intervention MeSH terms: Abiraterone Acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No
Keywords: prostate cancer; prostate; androgen independent prostate cancer (AIPC); androgen-independent; androgen independent; hormone insensitive; hormone-insensitive; prostate specific antigen (PSA); prostatic adenocarcinoma; hormone-refractory; hormone refractory; hormone refractory prostate cancer (HRPC); immune therapy; immunotherapy; vaccine; dendritic cells; antigen-presenting cells; antigen presenting cells; cancer vaccine; therapeutic vaccine; therapeutic cancer vaccine; recombinant; biological; biopharmaceutical; biotechnology; biotech; castration resistant prostate cancer (CRPC); castration-resistant prostate cancer (CRPC); castration-resistance; sipuleucel-T; abiraterone; prednisone; sequence; sequencing

Summary:

      The purpose of this study was to evaluate the impact of concurrent versus sequential
      administration of abiraterone acetate plus prednisone on the ability to manufacture
      sipuleucel-T (by assessing sipuleucel-T product parameters), and to assess the safety and
      efficacy of sipuleucel-T with concurrent or sequential administration of abiraterone acetate
      plus prednisone in men with metastatic castrate resistant prostate cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  histologically documented prostate cancer confirmed by a pathology report from
             prostate biopsy or radical prostatectomy specimen

          -  metastatic status as evidenced by imaging obtained </= 56 days prior to registration
             demonstrating bone metastasis or lymph node metastasis

          -  castrate resistant prostate cancer: castrate levels of testosterone (</= 50 ng/dL);
             evidence of disease progression concomitant with surgical or medical castration

          -  serum PSA >/= 2.0 ng/mL

          -  castrate levels of testosterone (</= 50 ng/dL) achieved via medical or surgical
             castration

          -  baseline Eastern Cooperative Oncology Group (ECOG) performance status of </= 1

          -  systolic blood pressure (BP) </= 140 mm Hg and diastolic BP </= 90 mm Hg at screening

          -  adequate baseline hematologic, renal, and liver functions

          -  must live in a permanent residence within a comfortable driving distance (round trip
             within one day) of the clinical trial site

        Exclusion Criteria:

          -  the presence of known lung, liver, or brain metastases, malignant pleural effusions,
             or malignant ascites

          -  New York Heart Association Class III or IV heart failure

          -  any medical condition that may be compromised by increases in blood pressure,
             hypokalemia, or fluid retention

          -  Child-Pugh Class B or C hepatic insufficiency

          -  spinal cord compression, imminent long bone fracture, or any other condition likely to
             require radiation therapy and/or steroids for pain control

          -  known adrenalcortical insufficiency

          -  any medical contraindications to receiving prednisone

          -  prior treatment with sipuleucel-T

          -  previous treatment with abiraterone acetate (Zytiga(R)) or ipilimumab (Yervoy(TM))

          -  a requirement for systemic immunosuppressive therapy for any reason. Use of inhaled,
             intra-nasal, intra-articular, and topical steroids was allowed.

          -  treatment with any investigational vaccine or immunotherapy

          -  treatment with any chemotherapy prior to registration.

          -  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.

          -  myocardial infarction or ventricular or atrial arrhythmia within 6 months prior to
             registration

          -  ongoing anti-androgen withdrawal response.

          -  systemic steroid use within ≤ 60 days of registration

          -  treatment with denosumab (Xgeva(R) or Prolia (R)) within ≤ 3 months prior to
             registration

          -  positive test for human immunodeficiency virus (HIV) or human T cell lymphotrophic
             virus (HTLV) infections. Subjects with a positive test for hepatitis B or hepatitis C
             were allowed provided they meet the liver function test (LFT) criteria and have no
             signs of acute infection or active disease.

          -  treatment with any of the following medications or interventions within 28 days prior
             to registration: external beam radiation or major surgery requiring general
             anesthetic; saw palmetto; megestrol acetate (Megace(R)), diethylstilbestrol, and
             cyproterone; 5-alpha-reductase inhibitors (e.g. finasteride [Proscar(R)], dutasteride
             [Avodart(R)]); steroidal anti-androgen therapy; any other systemic therapy for
             prostate cancer, except for medical castration; treatment with any other
             investigational product for prostate cancer; substrates of CYP2D6 (e.g. including but
             not limited to thioridazine); inhibitors of CYP3A4 (e.g. including but not limited to
             ketoconazole, itraconazole, clarithromycin, nefazodone, telithromycin, and
             voriconazole); inducers of CYP3A4 (e.g. including but not limited to phenytoin,
             carbamazepine, rifampin, rifapentine, and phenobarbital)

          -  a requirement for treatment with opioid analgesics within 21 days prior to
             registration

          -  an active infection or infection requiring parenteral antibiotic therapy or causing
             fever within 7 days of registration

          -  any medical intervention, or other condition, or any other circumstance that, in the
             opinion of the Investigator or the Dendreon Medical Monitor, could compromise
             adherence with study requirements or otherwise compromise the study's objectives