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

NCT04097002 | Unknown Phase 1 DMC

• 3 other identifiers: CP-ORCA-010-02-CA2017-002737-39HC6-024-C227843
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

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.

Conditions

Adenocarcinoma of the Prostate

Keywords

Prostate cancer; Intratumoral; ORCA; Adenovirus; Localized Prostate cancer; Intraprostatic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Biological activity of ORCA-010

  365 days

• Antitumor immune responses

  365 days

• Shedding of ORCA-010

  365 days

Study Arms (4)

Phase I, Part A, Cohort 1

EXPERIMENTAL

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.

Biological: ORCA-010

Phase I, Part A, Cohort 2

EXPERIMENTAL

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.

Biological: ORCA-010

Phase I, Part A, Cohort 3

EXPERIMENTAL

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.

Biological: ORCA-010

Phase IIa, Part B, Cohort 4

EXPERIMENTAL

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.

Biological: ORCA-010

Interventions

ORCA-010 BIOLOGICAL

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.

Phase I, Part A, Cohort 1; Phase I, Part A, Cohort 2; Phase I, Part A, Cohort 3; Phase IIa, Part B, Cohort 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: Treatment naïve men diagnosed with adenocarcinoma of the prostate,
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Orca Therapeutics B.V.: lead
• CMX Research: collaborator

Study Sites (5)

Jonathan Giddens Medicine Professional Corporation

Brampton, Ontario, L6T 4S5, Canada

Location

G. Kenneth Jansz Medicine Professional Corporation

Burlington, Ontario, L7N 3V2, Canada

Location

Research St. Joseph's - Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

The Fe/Male Health Centres Recruiting

Oakville, Ontario, L6H 3 P1, Canada

Location

Urology and Male Infertility Clinic

Scarborough Village, Ontario, M1S 4V5, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• Cornelis Groen, BSc Law, PhD

  Orca Therapeutics B.V.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: September 20, 2019
• Study Start: November 12, 2019
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: October 31, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)