First in Man Clinical Study to Evaluate Safety and Tolerability of an Oncolytic Adenovirus in Prostate Cancer Patients.

Adenocarcinoma of the Prostate Clinical Trial

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04097002
• Other study ID #: CP-ORCA-010-02-CA
• Secondary ID: 2017-002737-39HC
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 12, 2019
• Est. completion date: December 2024

Study information

• Verified date: October 2023
• Source: Orca Therapeutics B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 24
• Est. completion date: December 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma of the Prostate
• Prostatic Neoplasms

Intervention

Biological:
• ORCA-010
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.

Locations

Country	Name	City	State
Canada	Jonathan Giddens Medicine Professional Corporation	Brampton	Ontario
Canada	G. Kenneth Jansz Medicine Professional Corporation	Burlington	Ontario
Canada	Research St. Joseph's - Hamilton	Hamilton	Ontario
Canada	The Fe/Male Health Centres Recruiting	Oakville	Ontario
Canada	Urology and Male Infertility Clinic	Scarborough	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Orca Therapeutics B.V.	CMX Research

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety profile of ORCA-010	To evaluate safety and tolerability of intratumoral administration of ORCA-010 according to CTCAE V5.0. The primary endpoint of this study is to assess Dose Limiting Toxicities (DLTs) and the Maximum Tolerated Dose (MTD) for ORCA-010 to determine the final safety dose of administration for Phase IIa/Part B.	365 days
Secondary	Biological activity of ORCA-010	To explore the biological activity of intratumoral administration of ORCA-010. Biological activity of ORCA-010 will be measured by assessing viral replication by measuring ORCA-010 virus DNA in blood. In addition, virus replication and spread will be assessed by staining prostate cancer tissue obtained through prostate biopsies with adenovirus specific antibodies. Subject's serum will be assayed for antibody responses against ORCA-010.	365 days
Secondary	Antitumor immune responses	To evaluate potential antitumor immune responses following ORCA-010 administration. Subject's serum will be analyzed for antibody responses against tumor-associated antigens (e.g. PSA, PSMA, PCA3, and Prostein). Subject's Peripheral Blood Mononuclear Cells (PBMCs) will also be analyzed for cellular immune responses against tumor-associated antigens.; Prostate biopsies will be taken to detect local antitumor immunological reactions (eg. infiltration and activation of T cells).	365 days
Secondary	Shedding of ORCA-010	Shedding of ORCA-010 will be assessed by detection of vector DNA in blood and urine using quantitative-PCR (Q-PCR).	365 days