Study of ODX (Osteodex) in Metastatic Castration Resistant Prostate Cancer (CRPC)

A Randomised, Double-blind, Dose Finding, Repeat Dose Phase II Multicentre Study of ODX for the Treatment of Patients With Castration Resistant Prostate Cancer (CRPC) and Skeletal Metastases

This is a phase II randomised, double-blind, dose finding, repeat dose Phase II multicentre study of ODX for the treatment of patients with castration resistant prostate cancer (CRPC) and skeletal metastases.

The primary objective is to evaluate the relative change from baseline in response markers related to bone metabolism (alkaline phosphatase (B-ALP) and S P1NP) at 12 weeks of three different doses of ODX (3.0, 6.0 and 9.0 mg/kg ODX).

Males, diagnosed with CRPC, who fulfil the inclusion criteria and does not have any exclusion criteria, will be asked to participate in the study. The subject will be informed orally and in writing about the study procedures and give written informed consent, prior to study start.

At the screening visit the following examinations are performed: Physical examination, medical history and concomitant medication. Heart rate, blood pressure, weight, height, body temperature and respiratory rate are measured. Blood samples are drawn and urine sample is collected. ECG is recorded. Bone scan and diagnostic CT scan are also performed. At the next visit, baseline, the subject is examined physically and heart rate, blood pressure, weight, body temperature and respiratory rate are measured, ECG is recorded, blood samples drawn and urine sample collected. FACT-P and EQ-5D-5L (European Quality of Life - 5 Dimensions with 5 levels) questionnaire are filled out by the subject. Adverse events and concomitant medication is documented and the first dose of the investigational product is given.

The subject is surveyed for 3 hours at the hospital.

The duration of the study for the individual subject will be approximately 20 weeks from screening to the follow-up visit 2 weeks after the last dose. Each subject will receive 10 doses of investigational product. After the follow-up visit, the subject enters to long-term follow-up phase which lasts approximately 2 years.

A Data Monitoring Committee (DMC) will be designated and will be responsible to monitor/review all study related safety data. After review of safety data the DMC will provide recommendation as to whether the dose escalation can proceed as planned according to the protocol.

Inclusion Criteria:

1. Age ≥18 years at the time of signing the informed consent form

2. Histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate

3. Evidence of disease progression based on changes in metastatic bone disease (≥2 bone lesions compared to a prior examination) in bone scan and/or other imaging modality AND/OR evidence of PSA progression in the three consecutive determinations at minimum of 1 week intervals

4. Castrate level of serum testosterone ≤1.7 nmol/L

5. Performance status ECOG 0-2

6. Laboratory requirements:

   Haematology:

   Neutrophils ≥ 1.5 x 109/l Haemoglobin ≥ 90 g/l Platelets ≥ 100 x 109/l

   Hepatic function:

   Total S-bilirubin ≤ 1.5 times the upper limit of normal (ULN) AST (SGOT) / ALT (SGPT) ≤ 2.5 times ULN or ≤ 5 times ULN in patients with known liver metastases

   Renal function:

   S-creatinine (S-Cr)≤ 1.5 times ULN

7. No evidence (≤ 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin)

8. Able to adhere to the study visit schedule and other protocol requirements Life expectancy ≥6 months

Exclusion Criteria:

1. Concurrent use of other anti-cancer agents or treatments, with the following exception: a stable dose of Luteinizing Hormone-Releasing Hormone (LHRH) agonist/antagonist or polyestradiol phosphate. Washout period: bicalutamide 6 weeks; flutamide 4 weeks; abiraterone / enzalutamide 6 weeks, chemotherapy 4 weeks; Radium-223 4 weeks; Strontium-89 or Samarium-153 6 months.
2. Any treatment modalities involving palliative radiation therapy or major surgery within 4 weeks prior to treatment in this study
3. Simultaneous participation in any other study involving investigational drugs or having participated in a study less than 4 weeks prior to start of study treatment
4. Any condition, including the presence of laboratory abnormalities, which confounds the ability to interpret data from the study or places the patient at unacceptable risk if he participates in the study
5. Known brain metastases
6. Dental surgery (dental extraction), periodontal disease, local trauma including poorly fitting dentures within 6 months prior to the first dose of study drug
7. Treatment with bisphosphonates or denosumab within 4 weeks prior to first dose of study medication