Provenge Followed by Docetaxel in Castration-Resistant Prostate Cancer

Inclusion Criteria:

Male 18 years and older.
Pathologic confirmation of prostate adenocarcinoma.
Asymptomatic or minimally symptomatic disease.
Presence of skeletal or visceral/nodal metastasis confirmed by MRI, scintigraphy, or CT scan

Disease progression as indicated by:

PSA increase indicated by two consecutive higher values over baseline at assessments performed at least 7 days apart from each other in the previous 28 days with the absolute value ≥5 ng/ml; OR
Progression of measurable lymph nodes (≥15 mm) measureable per RECIST v1.1 criteria; OR
New bone lesions appearing on imaging compared with a prior bone scan. (Bone scan to be performed at screening or within the previous 28 days.)
Maintenance of castrate conditions: Patients who have not had a surgical orchiectomy must continue with hormone therapy (GnRH/LHRH agonists or antagonists) to maintain levels of serum testosterone of <50 ng/dl.
Patient is clinically immunocompetent. Clinical immunocompetence will be assumed unless a subject has been diagnosed as being immunosuppressed, is receiving oral steroids (nasal sprays and inhalers are permitted), or is receiving immunosuppressive therapy following transplant, in which case they will be excluded.
Peripheral neuropathy grade ≤1.

Laboratory criteria:

Adequate bone marrow function:

White blood cells ≥4000/mm3
Absolute neutrophil count ≥1500/mm3
Absolute lymphocyte count ≥500/µl
Hemoglobin ≥10 g/dl
Platelet count ≥100,000/mm3
Total bilirubin within normal limits (benign hereditary hyperbilirubinemias, e.g., Gilbert's syndrome, are permitted)
Renal function creatinine ≤1.5 x ULN
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be within normal range.
Life expectancy of at least 6 months based on Investigators' judgment
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
At least 4 weeks after surgery or radiotherapy
If patients have been receiving bisphosphonate or denosumab, they can continue either medication.
Sufficient washout period from previous anti-androgen and hormonal therapies (PSA regression verification required after casodex withdrawal during the 6-week washout period).
Patient is willing and available to attend clinic visits at least every 2 weeks.
Signed, informed consent, including patient's ability to comprehend its contents

Exclusion Criteria:

Patient's disease burden is greater than the prognostic criteria defined earlier, including the presence of visceral or bone metastases.
Patient has "currently active" second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy if they have completed therapy >5 years previously and have no known evidence of residual or recurrent disease.
Current symptomatic cord compression requiring surgery or radiation therapy
Prior chemotherapy for prostate cancer

Patient is using supplements or complementary medicines/botanicals. Patients should review the label with their doctor prior to enrolment. The following exceptions are permitted at screening and during the course of the study.

Conventional multivitamin supplements
Selenium
Lycopene
Soy supplements
Vitamin E
Fish oil supplements
Vitamin D
Glucosamine supplements
Age-related eye disease vitamins
Ginkgo biloba

Patient co-morbidities:

HIV positive
Acute hepatitis B (HBV) or active hepatitis C (HCV)
Clinical and laboratory evidence of active bacterial, viral, or fungal infection requiring systemic treatment

Clinically significant cardiovascular disease including

Symptomatic congestive heart failure
Unstable angina pectoris
Serious cardiac arrhythmia requiring medication
Uncontrolled hypertension >150/100mm Hg (if controlled with medication this is not an exclusion).
Hypotension
Myocardial infarct or ventricular arrhythmia or stroke within a 6-month period prior to inclusion, ejection fraction (EF) <40%, or serious cardiac conduction system disorders
Patient is exhibiting evidence of symptomatic congestive heart failure, pulmonary embolus, vascular thrombosis, transient ischemic attack, cerebrovascular accident, unstable angina, myocardial infarction or active ischemia if a pacemaker is not present on electrocardiogram (ECG). An ECG must be performed at screening unless the subject has measurable disease in which case an ECG taken prior to screening but within 28 days of start of treatment will be accepted.
Pleural and pericardial effusion of any CTCAE grade
Rheumatoid disease (asymptomatic subjects with controlled and rarely flaring rheumatoid arthritis are also excluded)
Peripheral neuropathy having a CTCAE grade ≥2
History of malignant disease (with the exception of non-melanoma skin tumors) in the preceding 5 years
Active autoimmune disease requiring treatment (except non-insulin-dependent diabetes mellitus)
History of severe forms of primary immune deficiencies
History of anaphylaxis or other serious reactions following vaccination
Uncontrolled co-morbidities including psychiatric or social conditions which, in the Investigator's opinion, would prevent participation in the trial
Patient has had major surgery or radiation therapy completed < 4 weeks prior to screening.
Patient has had prior exposure to the radiopharmaceuticals radium 223, strontium, or samarium within 8 weeks prior to screening.
Patient is receiving concurrent chemotherapy, immunotherapy, radiotherapy, or investigational agents.
Patient has cerebral metastases (known from previous investigations or clinically detectable).
Patient has serum testosterone >50 ng/dl.
Systemic corticosteroids at doses >40 mg hydrocortisone daily or equivalent for any reason other than (a) prescribed as replacement therapy in the case of adrenal insufficiency or (b) oral dexamethasone administration used in combination with docetaxel.
Patient has in the opinion of the physician a serious or uncontrolled intercurrent infection or non-malignant medical illness which is uncontrolled.
Systemic immunosuppressive therapy for any reason.
Treatment with anti-androgens, inhibitors of adrenal-produced androgens (abiraterone), androgen receptor inhibitors (enzalutamide), or other hormonal tumor-focused treatment performed on the day of screening or within the previous 4 weeks, including any dose of megestrol acetate, finasteride, any herbal product known to decrease PSA levels (e.g., saw palmetto and PC-SPES), or any systemic corticosteroid must discontinue the agent for at least 4 weeks prior to screening. Progressive disease (as defined above) must be documented after discontinuation of the therapy.
Refusal to sign the informed consent.
Participation in a clinical trial using experimental therapy within the last 60 days.