first in man clinical study to evaluate safety and tolerability of an oncolytic adenovirus in prostate cancer patients.

Conditions: Adenocarcinoma of the Prostate

Summary: this open label, dose escalating study is a phase i/iia first in man study designed to evaluate the safety and tolerability of intratumoral administration of a novel oncolytic adenovirus (orca-010) in treating diagnosed treatment naïve patients with localized prostate cancer.

the study is divided into two parts. in part a of the study, cohorts of subjects will be administered escalating doses of orca-010, using the 3+3 design. when the maximum tolerated dose has been determined in part a, a group of 12 new subjects will be treated in part b of the study at this dose, with two administrations separated by a 2-week interval.

Eligibility criteria:
inclusion criteria: 1. histologically confirmed adenocarcinoma of the prostate, which is localized to the prostate ( within 24 months of screening) 2. absence of lymph node, bone or other metastases as determined by mri and ct scan, bone scan or nano-mri (≤3 months prior to first administration) 3. men between 18 and 75 years inclusive 4. ecog status 0 or 1 5. ability to understand and willingness to sign informed consent 6. adequate liver, renal and bone marrow function: ast \& alt \ 9.0 g/dl (5.59 mmol/l), platelet count \> 100x10\*9/l, neutrophils \> 1.5x10\*9/l, inr \< 1.5xuln 7. egfr ≥ 30 ml/min, using the cockcroft - gault equation: creatinine clearance = \[{(140 - age in years) x (weight in kg)} x 1.23\] /serum creatinine in mmol/l exclusion criteria: 1. tumor not accessible for injection 2. prior treatment of prostate cancer with radiation therapy or brachytherapy 3. prior use of chemotherapy/hormone therapy for treatment of cancer 4. target tumor adherent to a major vascular structure 5. participation in any investigational drug study within the last 12 months prior to first administration of orca-010 6. clinically significant active infection (viral or bacterial) 7. known immunosuppressive diseases (e.g. hiv, hepatitis b and c) 8. history of any other oncological malignancy, excluding basal cell carcinoma of the skin, in the past 5 years 9. not willing to refrain from sexual activities or use a double barrier contraceptive device (condom with foam or vaginal suppository, diaphragm with spermicide) after administration of orca-010 and until 42 days after the last orca-010 administration 10. severe obesity defined as body mass index (bmi) \> 30 kg/m2 11. positive for adenovirus in throat swap or serum as determined by pcr at screening 12. recent (within 3 months prior to enrolment in the study) history of alcohol abuse or other substances such as barbiturates, cannabinoids and amphetamines or a positive urine screen for drugs of abuse 13. use of medication known to have immunosuppressive effects, except topical/inhaled steroids under 10 mg/day prednisolone equivalent (see appendix 7) 14. use of systemic antiviral medication within 3 months prior to enrolment in the study 15. use of any anti-coagulants/blood thinner except for asa 81mg 16. any condition that in the opinion of the investigator could interfere with the conduct of the study 17. for part b only: subjects enrolled in part a of the study

Keywords: prostate cancer intratumoral orca adenovirus localized prostate cancer intraprostatic