First in Man Clinical Study to Evaluate Safety and Tolerability of an Oncolytic Adenovirus in Prostate Cancer Patients.
First in Man Clinical Study to Evaluate Safety and Tolerability of an Oncolytic Adenovirus in Prostate Cancer Patients.
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.
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 < 2.5 x ULN, total bilirubin
 < 1.5 x ULN, Alkaline phosphatase < 3 x ULN, Serum creatinine < 1.5 x ULN, Haemoglobin
 > 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