ELUCIDATE: Enabling Lung Cancer Identification Using Folate Receptor Targeting (Elucidate)

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Neoplasms; Lung Cancer
• Intervention / Treatment: Device: Near infrared camera imaging system; Drug: OTL38 for Injection

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Stamford, Connecticut, United States, 06904
      • Stamford
  • Iowa
    • Iowa City, Iowa, United States, 55242
      • University of Iowa
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98109
      • Swedish Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and Female subjects 18 years of age and older
2. Have a primary diagnosis, or a high clinical suspicion, of cancer in the lung warranting surgery based on CT/PET or other imaging
3. Are scheduled to undergo surgical thoracoscopy for diagnostic wedge resection followed by anatomic lung resection
4. 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
5. 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:

1. Previous exposure to OTL38
2. Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the subject
3. 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.
4. History of allergy to any of the components of OTL38, including folic acid
5. 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
6. Clinically significant abnormalities on electrocardiogram (ECG) at screening.
7. Presence of any psychological, familial, sociological condition or geographical challenges potentially hampering compliance with the study protocol and follow-up schedule
8. Impaired renal function defined as eGFR< 50 mL/min/1.73m2
9. 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.
10. Received an investigational agent in another investigational drug or vaccine trial within 30 days prior to the administration of study drug
11. Known sensitivity to fluorescent light

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: On Target Laboratories, LLC
• Collaborators: Clinipace Worldwide
• Investigators: Principal Investigator: Sunil Singhal, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2020
• Primary Completion (Actual): October 7, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: January 22, 2020
• First Submitted That Met QC Criteria: January 22, 2020
• First Posted (Actual): January 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2023
• Last Update Submitted That Met QC Criteria: February 23, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Intraoperative Imaging
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: OTL-2019-OTL38-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes