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

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.

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.