Anti-OX40, Cyclophosphamide (CTX) and Radiation in Patients With Progressive Metastatic Prostate Cancer

Inclusion Criteria:

1. Patients with measurable or evaluable metastatic adenocarcinoma of the prostate. Either histologic or cytologic diagnosis is acceptable
2. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Appendix A.)
3. Age 18 years old or above
4. Laboratory values (performed within 28 days prior to enrollment) as follows:

   * WBC ≥ 2000/microlitre
   * Serum creatinine \< 1.5 X upper limit of laboratory normal
   * Hgb \> 8g/dl (patients may be transfused to reach this level)
   * Platelets \> 100,000 cells/mm3
   * Total bilirubin \< 1.5 X upper limit of laboratory normal, unless due to Gilbert's disease
   * AST (SGOT) and ALT (SGPT) \< 2.5 X upper limit of laboratory normal
   * Alkaline phosphatase \< 2.5 X upper limit of laboratory normal (If alkaline phosphatase \> 2.5 X upper limit of laboratory normal due to bone metastases, then patient is eligible.)
   * HIV 1 and 2 antibody Negative
   * Hepatitis B surface antigen Negative
   * Hepatitis C antibody Negative
   * PSA \> 2 ng/ml
   * Testosterone \< 50 ng/ml
5. Confirmed radiographic and/or PSA progression (using PCWG2 definitions) after at least one androgen ablation regimen and docetaxel.Patients who refuse docetaxel chemotherapy or who are not candidates for docetaxel are eligible to enroll.
6. At least one bone metastatic lesion amenable to radiation
7. Ability to give informed consent and comply with the protocol. Patients with a history of psychiatric illness must be judged able to understand the investigational nature of the study and the risks associated with the therapy
8. No active bleeding
9. No clinical coagulopathy (INR \< 1.5, PT \< 16 seconds, PTT \< 38 seconds)
10. Anticipated lifespan greater than 12 weeks
11. Patients on LHRH agonists or bisphosphonates prior to study enrollment should continue these medications without change

Exclusion Criteria:

1. Active infection.
2. Active autoimmune disease.
3. Previous treatment with mouse monoclonal antibodies
4. Need for chronic maintenance oral steroids.
5. Active brain metastatic disease. Patients with treated brain metastases with surgery, gamma-knife radiosurgery or radiation and stable for at least 4 weeks and off steroids are eligible.
6. Any medical or psychiatric condition that in the opinion of the PI would preclude compliance with study procedures.