Safety and Tolerability of NOX66 in Combination With Palliative Radiotherapy in Patients With Late-Stage Prostate Cancer

Inclusion Criteria:

1. Provision of informed consent
2. ≥ 18 years of age
3. Histologically confirmed prostate cancer and/or PSA of \>100 ng/mL at original diagnosis
4. Metastatic disease evidenced by either CT/MRI imaging or bone scan
5. Objective evidence of disease progression as defined by either:

   i. Radiographic progression of in nodal or visceral metastases and bone disease progression with 2 or more new lesions ii. Rising PSA value ≥2ng/ml in at least 3 measurements, at least 1 week apart, with castrate levels of serum testosterone.
6. Eligible to receive palliative radiation therapy for management of disease
7. At least one symptomatic lesion which is suitable for radiation therapy
8. ECOG Performance status 0-2
9. A minimum life expectancy of 24 weeks
10. Adequate bone marrow, hepatic and renal function as evidenced by:

    * Absolute neutrophil count (ANC) \> 1.5 x 109/L
    * Platelet count \> 100 x 109/L
    * Hemoglobin \> 9.0 g/dL
    * Serum bilirubin \< 1.5 x ULN
    * AST/ALT (SGOT/SGPT) \< 2.5 x ULN for the reference laboratory or \< 5 x ULN in the presence of liver metastases
    * Serum creatinine \< 1.5 x ULN
11. Ongoing androgen deprivation therapy with luteinizing hormone-releasing hormone (LHRH) agonist or antagonist
12. At least 4 weeks must have elapsed prior to commencement of NOX66 treatment since prior chemotherapy, investigational drug or biologic therapy and any toxicity associated with these treatments has recovered to ≤ NCI-CTCAE (version 4.03) Grade 1.
13. At least 21 days must have elapsed following major surgery and any surgical incision should be completely healed.

Exclusion Criteria:

1. Tumour involvement of the central nervous system
2. Uncontrolled infection or systemic disease
3. Clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease, angina, and cardiac arrhythmias) or myocardial infarction within the last 12 months

   • Patients with a QTc \> 470 msec on screening ECG
4. Concurrent systemic chemotherapy or biological therapy
5. Any situation where the use of suppository therapy is contra-indicated or impractical (eg. chronic diarrhoea, colostomy, ulcerative colitis).
6. Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated or both)
7. Any subject whose testosterone is not suppressed i.e. is \> 0.5nmols/L
8. Any other reason which, in the opinion of the investigator, will preclude suitable participation in the study.