A Phase 1b Dose Escalation Trial of PSK®/Placebo With Docetaxel to Treat Metastatic Castration-resistant Prostate Cancer

Inclusion Criteria:

Male patients 18 years or older
Histologically confirmed diagnosis of adenocarcinoma of the prostate
Evidence of metastatic disease by standard imaging studies (bone scan, Computerized Tomography Scan (CT) or Magnetic Resonance Imaging (MRI))
Testosterone levels <50 ng/dL

Confirmed progressive disease defined by one or more of the following:

an increase in PSA, > 2ng/dL x 2 or more values at least 1 week apart in the setting of metastatic disease
appearance of new bone lesions on bone scan
progression of soft tissue lesion defined by the Response Evaluation Criteria In Solid Tumors [RECIST] 1.1 criteria
Concurrent use of an agent for testosterone suppression (e.g., Luteinizing Hormone Releasing Hormone [LHRH] agonist) if the patient is not surgically castrate
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 determined within 28 days before enrollment
Recovery to CTCAE grade ≤ 1 toxicity, to patient's baseline status (except alopecia), or toxicities deemed irreversible from the effects of prior cancer therapy (CTCAEs grade > 1 that are not considered a safety risk by the investigator will be allowed)

Adequate bone marrow function defined as:

absolute neutrophil count (ANC) > 1500 cells/mm³ without growth factor support
platelet count > 100,000 cells/mm³ without transfusion or growth factor support
hemoglobin > 9g/dL without transfusion or growth factor support

Adequate liver function defined as:

total bilirubin < upper limit of normal (ULN)
alanine aminotransferase (ALT) < 1.5 x ULN
aspartate aminotransferase (AST) < 1.5 x ULN
Adequate renal function defined as serum creatinine level within normal limits (WNL)
At least a 6-month or greater life expectancy
Ability to understand and sign a written informed consent, which will be obtained from study participants before undergoing any study-specific procedures
Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures
Suitable venous access for the study-required blood sampling (i.e., including PK sampling)

Exclusion Criteria:

Prior treatment with antineoplastic chemotherapy or radioisotopes for metastatic disease
Prior adjuvant or neo-adjuvant chemotherapy within 12 months of study entry
Last dose of sipuleucel-T therapy within 4 weeks of enrollment
Any investigational therapies within 4 weeks of study entry
Radiotherapy within 4 weeks of study entry
Major surgery within 4 weeks of study entry, and not fully recovered to baseline or a stable clinical status
Uncontrolled high blood pressure (systolic blood pressure > 160mmHg, diastolic blood pressure > 95mmHg)
Receiving chronic steroid therapy. Topical and inhaled steroids are permitted
Known severe hypersensitivity reactions to docetaxel or other drugs formulated in polysorbate 80, or to mushroom products
Any comorbid condition or unresolved toxicity that would preclude administration of docetaxel
Medical contraindication to any docetaxel pre-medications
History of > grade 2 neurotoxicity or any toxicity from any cause that has not resolved to < grade 1
Brain or other CNS metastasis
The need for chronic daily immunosuppressive therapy, including concurrent use of prednisone
Evidence of active second malignancy, except non-melanoma skin cancer
Infection requiring intravenous antibiotic therapy or other severe infection within 14 days preceding first dose of study drug
Inability to swallow oral medication or maintain a fast, as required 2 hours before and 1 hour after PSK administration
Uncontrolled pain at baseline, impending complication from bone metastasis and/or presence of urinary obstruction
Other medical or psychiatric condition that may increase the risk associated with trial participation or any other condition in the judgment of the investigator that may interfere with the interpretation of trial results or would make the patient inappropriate for enrollment in this trial