IS-002 in Prostate Cancer

Study Overview
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Brief Summary
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Phase 2 randomized controlled multi-center study of IS-002, in conjunction with near-infrared (NIR) fluorescence imaging, for identification of prostate cancer during robotic-assisted radical prostatectomy (RARP) with (extended) pelvic lymph node dissection ((e)PLND) using the da Vinci® X/Xi Surgical System with Firefly® Fluorescence Imaging.

Official Title
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Phase 2 Multi-Center Randomized Controlled Feasibility Study of IS-002 in Subjects Undergoing Robotic-Assisted Radical Prostatectomy Using the da Vinci® Surgical System With Firefly® Fluorescence Imaging

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Administration of IS-002
* Device: Firefly fluorescent imaging
* Procedure: robotic-assisted laparoscopic prostatectomy with pelvic lymph node dissection


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Subjects aged 18 to 75. Subject has a confirmed adenocarcinoma of the prostate as defined by (histo-) pathology. Subject has CAPRA ≥6; or ≥T3 disease on imaging (TRUS and/or MRI); or a Gleason sum score ≥8; or regional lymphadenopathy suspicious for nodal metastases on imaging. Subject is scheduled to undergo robotic-assisted radical prostatectomy (RARP) with (extended) pelvic lymph node dissection ((e)PLND) using a da Vinci® X/Xi Surgical System equipped with Firefly® Fluorescence Imaging. Subject is willing and able to provide written informed consent. Subject can comply with the study procedures and study visits and understands an informed consent document. Exclusion criteria Subject has known bone metastasis. Subject has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Subject has a known history of acute or chronic liver or kidney disease. • Renal function at screening: i. Creatinine clearance: <50 mL/min as determined using the Cockcroft-Gault formula ii. Albumin: <LLN • Hepatic function at screening: i. AST and/or ALT: >2.5x ULN ii. Total Bilirubin (serum): >1.5x ULN Subject has received neo-adjuvant therapy, radiation therapy, focal ablation therapy, hormonal therapy, or androgen deprivation therapy within the last 4 months. Subject is currently receiving an investigational therapeutic agent; or has participated in a study of an investigational therapeutic agent within the past 6 months prior to the day of IS-002 infusion; or is involved in a significant risk investigational device study within the past 6 months prior to the day of IS-002 infusion. Subject has any other condition or personal circumstance that, in the judgment of the site Investigator, might interfere with the collection of complete quality data or represents an unacceptable safety profile.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: RARP + IS-002<br>Subjects will receive IS-002, but during surgery NO fluorescence imaging will be performed. | Drug: Administration of IS-002<br>* Intravenous administration of IS-002 approximately 24 hours prior to surgery<br>Procedure: robotic-assisted laparoscopic prostatectomy with pelvic lymph node dissection<br>* Subject will undergo robotic-assisted laparoscopic prostatectomy with pelvic lymph node dissection<br>* Other names: RARP;|
| Experimental: RARP + IS-002 + intraoperative near-infrared imaging<br>Subjects will receive IS-002, and during surgery fluorescence imaging will be performed. | Drug: Administration of IS-002<br>* Intravenous administration of IS-002 approximately 24 hours prior to surgery<br>Device: Firefly fluorescent imaging<br>* Near-infrared fluorescence imaging using Firefly technology will allow fluorescence imaging of IS-002<br>Procedure: robotic-assisted laparoscopic prostatectomy with pelvic lymph node dissection<br>* Subject will undergo robotic-assisted laparoscopic prostatectomy with pelvic lymph node dissection<br>* Other names: RARP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with ≥1 positive surgical margins (PSMs) on final histopathologic assessment in the Intervention arm and the Control arm. | The proportion of subjects with ≥1 PSMs on final histopathologic assessment in the Intervention arm and the Control arm. | Within 3 months post-surgery | 
| The mean number of positive surgical margins (PSMs) on final histopathologic assessment in the Intervention arm and the Control arm. | The mean number of PSMs on final histopathologic assessment in the Intervention arm and the Control arm. | Within 3 months post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic performance of IS-002 fluorescence | The key secondary outcome is the determination of false-positive, true-positive, false-negative and true-negatives rates. | Up to 1 year post-surgery | 
| Safety: Adverse event assessment | Incidence of treatment-emergent adverse events from time of IS-002 administration through study exit using CTCAE v5.0 | Up to 1 year post-surgery | 
| Pharmacokinetics: Area under the concentration-time curve (AUC) | Area under the concentration-time curve (AUC) from time zero to the time of the last measurable concentration as calculated by linear up/log down trapezoidal method (AUC0-last) | Up to 24 hours post-IS-002 administration | 
| Time to biochemical recurrence (BCR) | Time to BCR in the Intervention arm and the Control arm. BCR is defined a PSA level >0.1 ng/mL as determined by an ultrasensitive PSA assay. | Up to 1 year post-surgery | 
| Time to secondary treatment initiation | Time to secondary treatment(s) for prostate cancer in the Intervention arm and the Control arm. | Up to 1 year post-surgery | 
| Number of intraoperative fluorescent lymph nodes that are tumor positive that would not have been resected if the surgeon would have had access to white light imaging only | In the Intervention arm, the number of intraoperative fluorescent lymph nodes, per subject and per lymph node basin, that are tumor positive that would not have been resected if the surgeon would have had access to white light imaging only. | Up to 3 months post surgery |