ELUCIDATE: Enabling Lung Cancer Identification Using Folate Receptor Targeting

Study Overview
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Brief Summary
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This is a phase 3, multi-center, single dose, open-label, exploratory study in suspected lung cancer patients scheduled to undergo endoscopic or thoracic surgery per CT/PET/MRI or other imaging based on standard of care. This study aims to assess the efficacy of OTL38 and Near Infrared Imaging (NIR) at identifying pulmonary nodules within the operating theater, and to assess the safety and tolerability of single intravenous doses of OTL38.

Official Title
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A Phase 3, Randomized,Single Dose, Open-Label Study to Investigate the Safety and Efficacy of OTL38 Injection for Intraoperative Imaging of Folate Receptor Positive Lung Nodules

Conditions
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Lung Neoplasms, Lung Cancer

Intervention / Treatment
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* Drug: OTL38 for Injection
* Device: Near infrared camera imaging system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and Female subjects 18 years of age and older Have a primary diagnosis, or a high clinical suspicion, of cancer in the lung warranting surgery based on CT/PET or other imaging Are scheduled to undergo surgical thoracoscopy for diagnostic wedge resection followed by anatomic lung resection Female subjects of childbearing potential or less than 2 years postmenopausal agree to use an acceptable form of contraception from the time of signing informed consent until 30 days after study completion Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments Exclusion Criteria: Previous exposure to OTL38 Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the subject History of anaphylactic reactions to folate, including synthetic folic acid (pteroylmonoglutamic acid) and contrast agents containing indocyanine green for near infrared imaging. Subjects with a medical history of 'idiopathic anaphylaxis' will require evaluation. History of allergy to any of the components of OTL38, including folic acid A positive serum pregnancy test at Screening or a positive urine pregnancy test on the day of surgery or day of admission for female subjects of childbearing potential Clinically significant abnormalities on electrocardiogram (ECG) at screening. Presence of any psychological, familial, sociological condition or geographical challenges potentially hampering compliance with the study protocol and follow-up schedule Impaired renal function defined as eGFR< 50 mL/min/1.73m2 Impaired liver function defined as values > 3x the upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >2x ULN for total bilirubin except in subjects with Gilbert's syndrome. Received an investigational agent in another investigational drug or vaccine trial within 30 days prior to the administration of study drug Known sensitivity to fluorescent light

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Near-Infrared Imaging group<br>All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging. | Drug: OTL38 for Injection<br>* Folate analog ligand conjugated with an indole cyanine-like green dye as a solution in vials containing 3 mL at 2 mg/mL<br>* Other names: CYTALUX™ (pafolacianine) injection;Device: Near infrared camera imaging system<br>* Near infrared camera imaging system<br>|
| Other: No Imaging Group<br>All patients in this arm will receive OTL38 for injection but will not receive intraoperative imaging. | Drug: OTL38 for Injection<br>* Folate analog ligand conjugated with an indole cyanine-like green dye as a solution in vials containing 3 mL at 2 mg/mL<br>* Other names: CYTALUX™ (pafolacianine) injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Significant Events (CSE) | The primary efficacy endpoint is the proportion of patients who demonstrate at least one CSE as a result of utilizing OTL-38 and Near Infrared Imaging. | 1 day | 
| Localization of Primary Nodule | Proportion of FAS subjects with one or more primary NIR fluorescence positive lung nodules (cancerous or non-cancerous, excluding normal lung parenchyma) not detected under normal light and/or palpation | 1 day | 
| Identification of Cancerous Synchronous Lesions | The proportion of FAS subjects with one or more NIR fluorescence positive cancerous synchronous lesions not detected under normal light and/or palpation | 1 day | 
| Positive Resection Margins | The proportion of FAS subjects with the identification of a cancerous positive margin that fluoresces within (less than or equal to) 10 mm of the surgical resection staple line | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity for Cancerous Primary Nodules and Synchronous Lesions in FAS Subjects | Sensitivity or True Positive Rate (TPR) for OTL38 used with fluorescent light in FAS subjects, defined as the proportion of fluorescent light positive primary nodules and synchronous lesions that are histologically confirmed to be cancer relative to the total number of primary nodules and synchronous lesions confirmed to be cancer. | 1 day | 
| False Positive Rate for Cancerous Primary Nodules and Synchronous Lesions in FAS Subjects | False Positive Rate (FPR) for OTL38 used with fluorescent light in FAS subjects, defined as the proportion of fluorescent light positive primary nodules and synchronous lesions that are histologically confirmed not to be cancer relative to the total number of fluorescent light positive primary nodules and synchronous lesions | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intraoperative Imaging