Clinical trial NCT04097002: First in Man Clinical Study to Evaluate Safety and Tolerability of an Oncolytic Adenovirus in Prostate Cancer Patients.
Official title: A Phase I/IIa Study Evaluating the Safety and Tolerability of Intratumoral Administration of ORCA-010 in Treatment-Naïve Patients With Localized Prostate Cancer.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Adenocarcinoma of the Prostate
Keywords: Prostate cancer
Intratumoral
ORCA
Adenovirus
Localized Prostate cancer
Intraprostatic
Lead sponsor: Orca Therapeutics B.V.
Sponsor class: INDUSTRY
Collaborators: name: CMX Research
First posted: 2019-09-20
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase I and Phase IIa.

Phase I/ Part A is a Single-escalated dose of ORCA-010 (3 dose cohorts) to determine the Maximum Tolerated Dose.

Phase IIa/ Part B is a two administration dose cohort at Maximum Tolerated Dose.
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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 \< 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

Primary outcomes:
measure: Safety profile of ORCA-010
timeFrame: 365 days
Secondary outcomes:
measure: Biological activity of ORCA-010
timeFrame: 365 days
measure: Antitumor immune responses
timeFrame: 365 days
measure: Shedding of ORCA-010
timeFrame: 365 days
Other outcomes:
Locations:
city: Brampton
country: Canada
facility: Jonathan Giddens Medicine Professional Corporation
state: Ontario
city: Burlington
country: Canada
facility: G. Kenneth Jansz Medicine Professional Corporation
state: Ontario
city: Hamilton
country: Canada
facility: Research St. Joseph's - Hamilton
state: Ontario
city: Oakville
country: Canada
facility: The Fe/Male Health Centres Recruiting
state: Ontario
city: Scarborough
country: Canada
facility: Urology and Male Infertility Clinic
state: Ontario
Study officials:
affiliation: Orca Therapeutics B.V.
name: Cornelis Groen, BSc Law, PhD
role: STUDY_DIRECTOR
References: