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

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ClinicalTrials.gov Identifier: NCT04097002
Recruitment Status : Not yet recruiting
First Posted : September 20, 2019
Last Update Posted : September 23, 2019
Sponsor:
Collaborator:
CMX Research
Information provided by (Responsible Party):
Orca Therapeutics B.V.

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.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Prostate Biological: ORCA-010 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
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.

Masking: None (Open Label)
Primary Purpose: Treatment
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.
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Phase I, Part A, Cohort 1

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
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.

Experimental: Phase I, Part A, Cohort 2

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
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.

Experimental: Phase I, Part A, Cohort 3

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
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.

Experimental: Phase IIa, Part B, Cohort 4

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
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.




Primary Outcome Measures :
  1. Safety profile of ORCA-010 [ Time Frame: 365 days ]
    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.


Secondary Outcome Measures :
  1. Biological activity of ORCA-010 [ Time Frame: 365 days ]
    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.

  2. Antitumor immune responses [ Time Frame: 365 days ]

    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).


  3. Shedding of ORCA-010 [ Time Frame: 365 days ]
    Shedding of ORCA-010 will be assessed by detection of vector DNA in blood and urine using quantitative-PCR (Q-PCR).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Treatment naïve men diagnosed with adenocarcinoma of the prostate,
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04097002


Contacts
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Contact: Nada Dragicevic 9053381078 ext 225 ndragicevic@cmxres.com

Locations
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Canada, Ontario
Jonathan Giddens Medicine Professional Corporation Not yet recruiting
Brampton, Ontario, Canada, L6T 4S5
Contact: Sangeeta Madaan    905-874-0092    sangeetamadaan@gmail.com   
Principal Investigator: Jonathan Giddens, MD         
G. Kenneth Jansz Medicine Professional Corporation Not yet recruiting
Burlington, Ontario, Canada, L7N 3V2
Contact: Zena Al-Mudaris, MSc    905-681-9149    janszresearch@gmail.com   
Principal Investigator: G. Kenneth Jansz, MD         
Sub-Investigator: Janet Strome, MD         
The Fe/Male Health Centres Recruiting Not yet recruiting
Oakville, Ontario, Canada, L6H 3 P1
Contact: Rupi Dhaliwal    905-338-3130 ext 2    rdhaliwal@malehealth.com   
Contact: Djordje Adanja    905-338-3130    djoka54@yahoo.com   
Principal Investigator: Peter Incze, MD         
Sub-Investigator: Richard Casey, MD         
Urology and Male Infertility Clinic Not yet recruiting
Scarborough, Ontario, Canada, M1S 4V5
Contact: Anastasia Rubanovich    416-754-1017    anastasia.rubanovich@gmail.com   
Principal Investigator: Allan Abramovitch, MD         
Sponsors and Collaborators
Orca Therapeutics B.V.
CMX Research
Investigators
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Study Director: Cornelis Groen Orca Therapeutics B.V.

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Responsible Party: Orca Therapeutics B.V.
ClinicalTrials.gov Identifier: NCT04097002     History of Changes
Other Study ID Numbers: CP-ORCA-010-02-CA
2017-002737-39 ( EudraCT Number )
HC6-024-C227843 ( Other Identifier: Health Canada )
First Posted: September 20, 2019    Key Record Dates
Last Update Posted: September 23, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Not yet determined.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Orca Therapeutics B.V.:
Prostate cancer
Intratumoral
ORCA
Adenovirus
Localized Prostate cancer
Intraprostatic
Additional relevant MeSH terms:
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Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type