A Study of Sipuleucel-T With Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer

Study Overview
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Brief Summary
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This is a randomized, open-label study designed to assess the effects of sipuleucel-T when administered concurrently or sequentially with enzalutamide.

Detailed Description
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This is a randomized, open-label study designed to assess the effects of sipuleucel-T when administered concurrently or sequentially with enzalutamide. This study consists of 3 phases. The screening phase will begin at the completion of the informed consent process and continue through registration. The active phase will begin at registration and continue through the post-treatment visit (30 to 37 days following the last study treatment). The long term follow-up (LTFU) phase will begin after the post-treatment visit and will continue until the subject's death or until Dendreon terminates the study.

Official Title
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A Randomized, Open-label, Phase 2 Study of Sipuleucel-T With Concurrent Versus Sequential Administration of Enzalutamide in Men With Metastatic Castrate-Resistant Prostate Cancer

Conditions
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Metastatic Prostate Cancer

Intervention / Treatment
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* Biological: sipuleucel-T
* Drug: enzalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent provided prior to the initiation of study procedures. Age ≥ 18 years. Histologically documented adenocarcinoma prostate cancer confirmed by a pathology report from prostate biopsy or a radical prostatectomy specimen. Metastatic disease as evidenced by bone metastasis or lymph node metastasis. Castrate-resistant prostate cancer as demonstrated by one of the following: Prostate specific antigen progression. Progression of measurable disease. Progression of non-measurable disease by soft tissue disease or bone disease. Castration levels of testosterone (≤ 50 ng/dL) achieved via medical or surgical castration. Serum PSA (Prostate specific antigen) ≥ 2.0 ng/mL. Screening ECOG (The Eastern Cooperative Oncology Group )performance status ≤ 1 Adequate screening hematologic, renal, and liver function as evidenced by laboratory test results obtained ≤ 28 days prior to registration. Negative serology test for human immunodeficiency virus 1 and 2. Resides within driving distance (round trip within 1 day) of the clinical trial site for the duration of the active phase. Exclusion Criteria: The presence of known lung, liver, or brain metastases, malignant pleural effusions, or malignant ascites. Spinal cord compression, imminent long bone fracture, or any other condition that is likely to require radiation therapy and/or steroids for pain control during the active phase. History of stage 3 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 1 or 2 cancer must have been adequately treated and been disease free for ≥ 3 years at the time of registration. History of seizures or of predisposing factors for seizures. Child-Pugh Class C hepatic insufficiency. History of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T, GM-CSF or granulocyte colony stimulating factor (G-CSF). Previous treatment with sipuleucel-T or enrollment in a sipuleucel-T trial, regardless of whether the subject received sipuleucel-T or control. Previous treatment with enzalutamide. Previous treatment with abiraterone acetate. Previous treatment with ipilimumab. Previous treatment with ketoconazole other than topical use or for treatment of infections (e.g., oral thrush); most recent use must have been ≥ 7 days prior to registration. Previous treatment with any immunotherapy or investigational vaccine. A requirement for ongoing systemic immunosuppressive therapy. Use of inhaled, intranasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to prevent or treat IV contrast reactions are allowed. Previous treatment with chemotherapy for mCRPC, or chemotherapy for any reason ≤ 2 years prior to registration. Use of concomitant medications that may lower the seizure threshold or the use of antiseizure medications ≤ 1 year prior to registration. Received GM-CSF or G-CSF ≤ 90 days prior to registration. Ongoing non-steroidal antiandrogen withdrawal response. Any of the following medications or interventions ≤ 28 days prior to registration: Radiation therapy, either via external beam or brachytherapy. Any systemic steroid. Use of inhaled, intra-nasal, intra-articular, and topical steroids is allowed. Oral or IV steroids to prevent or treat IV contrast reactions are allowed. Any systemic therapy for prostate cancer, except for ADT (Androgen deprivation therapy). Any investigational product for prostate cancer. Major surgery requiring general anesthesia, with the exception of placement of central venous catheters. Inducers and inhibitors of cytochrome P450 (CYP) enzyme CYP2C8 (gemfibrozil and rifampin). Medications that are metabolized by CYP3A4, CYP2C9, or CYP2C19 that have a narrow therapeutic index. Inducers of CYP3A4 (including but not limited to phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, and phenobarbital). A requirement for treatment with opioid analgesics for cancer-related pain ≤ 21 days prior to registration. An active infection requiring parenteral antibiotic therapy or causing fever (temperature > 100.5˚ F or 38.1˚ C) ≤ 1 week prior to registration. Any medical intervention, any other condition, or any other circumstance which could compromise adherence with study requirements or otherwise compromise the study's objectives.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Concurrent Arm<br>Subjects will receive sipuleucel-T concurrently with enzalutamide (160 mg orally once daily). Enzalutamide treatment will start 2 weeks prior to the first leukapheresis and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. | Biological: sipuleucel-T<br>* 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).<br>* Other names: APC8015;Drug: enzalutamide<br>* Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.<br>* Other names: Xtandi;|
| Experimental: Sequential Arm<br>Subjects will receive sipuleucel-T followed by enzalutamide (160 mg orally once daily). Enzalutamide treatment will start approximately 10 weeks after the first infusion of sipuleucel-T and continue for 52 weeks or until disease progression or unacceptable toxicity, whichever occurs first. | Biological: sipuleucel-T<br>* 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).<br>* Other names: APC8015;Drug: enzalutamide<br>* Enzalutamide is an androgen receptor inhibitor. It is indicated for the treatment of patients with mCRPC who have previously received docetaxel. The enzalutamide dose used in this study will be 160 mg orally once daily.<br>* Other names: Xtandi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Evaluate Peripheral PA2024-specific T Cell Proliferation Response to Sipuleucel-T Over Time Via a T Cell Stimulation Index (SI). | PA2024-specific T cell proliferation responses over time will be compared between the concurrent arm and sequential arm using a repeated measurement mixed model analysis. The unit of analysis for the T cell proliferation data is the stimulation index, defined as the median 3H uptake of 3 wells exposed to antigen divided by the median 3H thymidine uptake of 3 wells exposed to media. The stimulation index will be log-transformed prior to analysis. | Each patient was followed for up to 52 weeks after the first dose of sipuleucel-T. Immune sample draws during the treatment period (Week 0 through Week 4) were to be performed at the patient's pre-leukapheresis visits (Pre-Leuk 2 and Pre-Leuk 3). |