A Phase I/IIa Study Evaluating the Safety and Tolerability of Intratumoral Administration of ORCA-010 in Treatment-Naïve Patients With Localized Prostate Cancer.
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Adenocarcinoma of the Prostate
- Sponsor
- Orca Therapeutics B.V.
- Enrollment
- 24
- Locations
- 5
- Primary Endpoint
- Safety profile of ORCA-010
- Status
- Active, not recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Outcomes
Primary Outcomes
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 Outcomes
- Biological activity of ORCA-010(365 days)
- Shedding of ORCA-010(365 days)
- Antitumor immune responses(365 days)