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

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).

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