Title
First in Man Clinical Study to Evaluate Safety and Tolerability of an Oncolytic Adenovirus in Prostate Cancer Patients.
A Phase I/IIa Study Evaluating the Safety and Tolerability of Intratumoral Administration of ORCA-010 in Treatment-Naïve Patients With Localized Prostate Cancer.
Phase
Phase 1/Phase 2Lead Sponsor
Orca Therapeutics B.V.Study Type
InterventionalStatus
Active, not recruitingIndication/Condition
Adenocarcinoma of the ProstateIntervention/Treatment
ORCA-010Study Participants
24This 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.
The investigational new drug ORCA-010 is a novel and improved oncolytic adenovirus based on the adenovirus serotype 5 (Ad5) genome. ORCA-010 replicates specifically in cancer cells and not in normal tissue cells. Its replication has been shown in a wide variety of cancer cell types, and it is not limited to prostate cancer.
Two dose administration of ORCA-010 seperated by 2 weeks, Dose Cohort 4: The Maximum Tolerated Dose depending on Phase I/ Part A results. Group of 12 subjects.
Single dose-escalation of ORCA-010, Dose Cohort 1: 1x10*11 viral particles. Single dose of ORCA-010 will be administered for the first subject only and all relevant safety data for this subject will be reviewed by the DSMB prior to enrolling additional subjects. After the DSMB review, subjects will be enrolled in groups of three (including the first subject) and assessed for safety and Dose-Limiting Toxicity (DLT) after a single dose of ORCA-010. Group of 3 subjects. Dose will be escalated to the next cohort based on safety and toxicity results from the 3 treated subjects to determine the Maximum Tolerated Dose, if not determined by this cohort.
Single dose-escalation of ORCA-010, Dose Cohort 2: 5x10*11 viral particles. Group of 3 subjects. Dose will be escalated to the next cohort based on safety and toxicity results from the 3 treated subjects to determine the Maximum Tolerated Dose, if not determined by this cohort.
Single dose-escalation of ORCA-010, Dose Cohort 3: 1.5x10*12 viral particles. Group of 3 subjects. Dose will be considered as the Maximum Tolerated Dose based on safety and toxicity results from the 3 treated subjects.
Inclusion Criteria:
Histologically confirmed adenocarcinoma of the prostate, which is localized to the prostate ( within 24 months of screening)
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)
Men between 18 and 75 years inclusive
ECOG status 0 or 1
Ability to understand and willingness to sign informed consent
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
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:
Tumor not accessible for injection
Prior treatment of prostate cancer with radiation therapy or brachytherapy
Prior use of chemotherapy/hormone therapy for treatment of cancer
Target tumor adherent to a major vascular structure
Participation in any investigational drug study within the last 12 months prior to first administration of ORCA-010
Clinically significant active infection (viral or bacterial)
Known immunosuppressive diseases (e.g. HIV, Hepatitis B and C)
History of any other oncological malignancy, excluding basal cell carcinoma of the skin, in the past 5 years
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
Severe obesity defined as Body Mass Index (BMI) > 30 kg/m2
Positive for adenovirus in throat swap or serum as determined by PCR at screening
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
Use of medication known to have immunosuppressive effects, except topical/inhaled steroids under 10 mg/day prednisolone equivalent (See Appendix 7)
Use of systemic antiviral medication within 3 months prior to enrolment in the study
Use of any anti-coagulants/blood thinner except for ASA 81mg
Any condition that in the opinion of the Investigator could interfere with the conduct of the study
For Part B only: Subjects enrolled in Part A of the study