Durvalumab With or Without Tremelimumab in Metastatic Castration Resistant Prostate Cancer

Inclusion Criteria

• Patients must have histologically confirmed adenocarcinoma of the prostate that is castrate resistant.
• Disease progression as defined as one or both of the following: PSA Progression: A rising PSA with 2 subsequent rises over a reference value (not necessarily consecutively), measured a minimum of one week apart. The PSA that confirms progression must have a value of ≥ 2 ng/ml (ug/L).

OR Objective Progression:

• RECIST 1.1
• PCWG 3 Criteria for bone progression
• Patients must be surgically or medically castrated, with testosterone levels of longest diameter; Lymph nodes by CT scan ≥ 15 mm --> measured in short axis
• Patients must be ≥ 18 years of age.
• ECOG performance status 0 or 1.
• Prior Therapy

Systemic Therapy:

0-1 prior regimen of cytotoxic chemotherapy in the CRPC setting is permitted.

Hormonal Therapy:

• Patients must be castrate resistant.
• Have failed/progressed on prior abiraterone and/or enzalutamide.
• Patients must have discontinued anti-androgens for at least 4 weeks prior to study entry (at least 6 weeks for bicalutamide).

Other therapy:

Prior treatment with other agents, such as tyrosine kinase or other targeted agents is permissible.

• Systemic corticosteroids are permitted at a dose equivalent to ≤10 mg prednisone daily and are only permitted for reasons other than prostate cancer treatment (ex: fatigue, anorexia, etc); topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are permitted.
• Bisphosphonates/denosumab are permitted for treatment of hypercalcemia, osteoporosis and skeletal-related events.

Immunotherapy:

Patients may not have received prior immune check point inhibitors (anti PDL1 and anti CTL-4). Vaccines and treatment with oncolytic viruses is permissible.

Patients must have recovered from all reversible toxicity related to prior systemic therapy (chemotherapy and hormone) and have adequate washout as follows:

Longest of one of the following:

• Two weeks;
• The longer of 30 days or 5 half-lives for investigational agents;
• Standard cycle length of standard therapies.

Radiation:

Prior external beam radiation or radium-223 is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and the date of randomization. Exceptions may be made for low-dose non-myelosuppressive radiotherapy after consultation with CCTG. Concurrent radiotherapy is not permitted. Prior strontium-89 at any time is not permitted

Prior Surgery:

Prior major surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed between any major surgery and date of randomization, and that wound healing has occurred.

• Laboratory Requirements (Must be done within 7 days prior to randomization):

Abs Neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L Hemoglobin ≥ 90 g/L Bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN ≤ 5.0 ULN (if patient has liver mets) Serum Creatinine < 1.25 x ULN or Creatinine clearance ≥ 40mL/min

• Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use male condom plus spermicide while on study and for 6 months after the last dose of durvalumab and tremelimumab, or for 3 months after the last dose of durvalumab alone. Female partners of a male subject must use a highly effective method of contraception throughout this period.
• Male patients should also refrain from donating sperm during the study and for 6 months after the last dose of durvalumab and tremelimumab or for 3 months after the last dose of durvalumab alone.
• Subjects should not donate blood while participating in this study, or for at least 90 days following the last infusion of durvalumab or tremelimumab.
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willin