Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Illuminare-1 at 3 dose levels in patients undergoing minimally invasive radical prostatectomy and bilateral pelvic lymph node dissection. Dose levels of the agent will be administered starting at 0.25mg/kg, with increases in dose between cohorts of no more than 0.5 mg/kg until a maximum dose of 2.25mg/kg is reached, if needed. At the dose identified to have the acceptable NMR and no associated DLTs, Illuminare-1 will be studied in up to 20 additional patients at this dose to optimize the imaging protocol and provide additional safety data.

Illuminare-1

The Storz PDD system will be used as the hardware system in this phase 1 study due to its proven safety profile.

Karl Storz D-Light C photodynamic diagnostic (PDD)

Timothy Donahue, MD

Vincent Laudone, MD

This study will test the safety of using Illuminare-1 during standard surgery for prostate cancer. The study researchers will test increasing doses of Illuminare-1 to find the dose that makes the nerve structures fluoresce (light up) but causes few or mild side effects. When the researchers find this dose, it will be tested in new groups of study participants to see whether surgery performed using Illuminare-1 guidance is better than surgery performed without intraoperative guidance. The researchers will also do tests to study the way the body absorbs, distributes, and gets rid of Illuminare-1. This study is the first to test Illuminare-1 in people. Illuminare-1 has received Fast Track designation from the US FDA.

This is a first-in-human, single-arm, open-label, dose-escalation phase I study to investigate the safety of Illuminare-1, a myelin-binding fluorescent small molecule in patients undergoing routine minimally invasive radical prostatectomy.

Fluorescent Imaging of Nerves With Illuminare-1 During Surgery

Phase I Trial of Real-Time Intraoperative Fluorescent Imaging of Nerve Structures Using Illuminare-1, A Novel Myelin-Binding Fluorophore

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Five patients will be observed at each dose level. If \> 20% of patients within a cohort experience a grade 2 or higher adverse event that is considered attributable to the drug and clinically significant, dose escalation will be stopped at that level, and the prior dose level will be considered the MTD. DLTs will be defined using NCI-CTCAE 5.0.

Illuminare Biotechnologies

Memorial Sloan Kettering Cancer Center

Symptoms and General Pathology

Anastomotic Leak

Postoperative Complications

Fluorescense imaging used to evaluate blood perfusion

Fluorescent Imaging

A serious complication to colorectal surgery is anastomotic leakage (AL). AL increases post-operative mortality, decreases long-term survival, reduces the functional result and reduces qual-ity of life. Studies suggest that performing an indocyanine-green enhanced fluorescent angi-ography (ICGeFA), blood perfusion in the bowel can be visualised. It is suggested that using this procedure the relative risk of AL is reduced about 54-67%.

With this project we wish to evaluate the feasibility of the procedure, and, if proven feasible, to plan further studies evaluating the procedure.

Colorectal cancer is one of the most common cancer-diagnosis in Denmark. In 2014, 5186 pa-tients with colorectal cancer were registered. 1674 patients had cancer in the rectum and 1316 in the sigmoid colon. 668 patients underwent surgery with low anterior resection (LAR) and primary anastomosis, and 850 patients had a sigmoid resection with primary anastomosis.

A serious complication is anastomotic leakage (AL). In 2014 a total of 67 (10%) patients were registered with AL.

In general AL increases the post-operative mortality, decreases long-term survival and reduces the functional result and thereby reduces quality of life.

Due to the possible severity of AL all measures possible should be taken to ensure an early diag-nosis and timely treatment, as this has been shown to reduce morbidity and mortality. The symp-toms of AL are uncharacteristic; the diagnosis cannot only rely on the development of clinical symptoms. However, specific clinical scoring symptoms, measuring C-reactive protein (CRP) and radiologic examinations are proven useful.

Treatment of AL varies with the degree of leakage, from conservative treatment with rectal lavage, endo-VAC therapy, drainage of abscesses, re-laparoscopy or laparotomy with a diverting stoma, and finally to break down the anastomosis and creating a temporary or permanent colostomy, all procedures with or without antibiotic treatment.

It is essential that surgeons continuously strive to improve the operative technique with regard to anastomosis construction. Many factors influence the anastomotic healing: instrumentation error, tension on the anastomosis, bacterial contamination, etc. An important factor to ensure most opti-mal conditions in anastomotic healing is to ensure sufficient blood-supply/oxygen tension.

The surgeon evaluate so-called surrogates of bowel perfusion (evaluation of colour, mesenteric pulsation and arterial bleeding) prior to form the anastomosis, but studies have demonstrated that surgeon's intraoperative judgment in predicting of anastomotic leakage AL has an extremely low sensitivity and specificity.

Studies suggest that performing an indocyanine-green enhanced fluorescent angiography (ICGeFA), the blood perfusion in the bowel can be visualised. It is suggested that by evaluating perfusion of bowel ends, and, if needed, doing a re-resection, the risk of anastomotic leakage can be diminished. It is suggested that evaluating the anastomosis with ICG-FA and revising the anas-tomosis if necessary, the relative risk reduction of AL is about 54-67%. Several studies in robotic and laparoscopic colorectal surgery, confirms feasibility of using ICGeFA, also showing promising results in evaluating the bowel perfusion. Most studies and a newly published systematic review conclude that there is great need for larger controlled studies or randomised trails.

The primary objective with this study is to evaluate the feasibility of using ICGeFA in colorectal surgery and to evaluate if the surgeon's interpretation is dose and time dependent. Secondary ob-jective is to establish a nationwide research team, joining all the Robotic Surgery Centres in Den-mark for future research.

Last we wish to identify the optimal design for a further study, evaluating whether ICG is a helpful tool in diminishing the risk of anastomotic leakage.

Indocyanine Green Fluorescent Imaging in Robotic Assisted Rectosigmoidal Resection; a Multicenter Assessment of Interobserver Variation and Comparison With Computer-based Pixel Analysis

Indocyanine Green Enhanced Fluorescent Angiography: Can it Predict Anastomotic Leakage (AL) After Recto-sigmoid Resection for Malignancy, and Are we Able to Evaluate the Findings? -A Small Multi-centre Trial Study

Primary surgeons peroperative evaluation of fluoresence

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fluorescent Imaging of Nerves With Illuminare-1 During Surgery	NCT04983862	Prostate Adenoc...	Illuminare-1 Karl Storz D-Li...	18 Years -	Memorial Sloan Kettering Cancer Center
Indocyanine Green Fluorescent Imaging in Robotic Assisted Rectosigmoidal Resection; a Multicenter Assessment of Interobserver Variation and Comparison With Computer-based Pixel Analysis	NCT04766060	Colorectal Canc... Anastomotic Lea...	Fluorescent Ima...	18 Years -	Odense University Hospital
Fluorescent Imaging of Nerves With Illuminare-1 During Surgery	NCT04983862	Prostate Adenoc...	Illuminare-1 Karl Storz D-Li...	18 Years -	Memorial Sloan Kettering Cancer Center

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