Intraoperative Imaging of Pulmonary Nodules by OTL38

The primary end-point of the study is to determine the sensitivity of OTL in identifying lung nodules when excited by an imaging probe. Investigators intend to enroll 300 lung cancer patients in this study. The study is focusing on patients presenting with suspected malignancies of the lung and pleura who are considered to be good surgical candidates.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: OTL38

Detailed Description

According to the World Health Organization, lung cancer is the most common cause of cancer-related death in men and women, and is responsible for 1.5 million deaths worldwide annually as of 2012. Surgery remains the best option for patients presenting with operable Stage I or II cancers, however the five year survival rate for these candidates remains at a dismal 73% for Stage I and 53% for Stage II. The high rates of local recurrence suggest that surgeons are unable to completely detect and remove primary tumor nodules in a satisfactory manner as well as lingering metastases in sentinel lymph nodes. By ensuring a negative margin through imaging during surgery it would be possible for the investigators to improve the rates of recurrence free patients and thus overall survival.

Thoracic malignancies are the ideal disease to investigate intra-operative imaging. Over 85% of lung and pleural malignancies express folate receptor alpha (FRA), therefore making folate receptors (FR) the ideal targets for imaging agents. While folate will initially distribute to all cells, redistribution, metabolism, and excretion will eliminate most of this agent from healthy tissues within hours. Tumor cells that over express FRα will retain folate and any fluorescent labeled folate conjugate and internalize this. It is important to note that FRA is expressed only in the proximal tubules of the kidneys, activated macrophages, and in the choroidal plexus. However, the fluorescence signal in the kidneys is expected to be significantly lower than the tumor tissues. Thus, the false positive detection rate is expected to be extremely low.

The investigators have conducted a Phase I clinical trial with folate-FITC in 50 patients with lung cancer. In the study at UPenn, the investigators had no adverse events. The investigators had excellent sensitivity and specificity with this technique with only grade 1 side effects (allergic reaction). All side effects reversed when the injection was halted. This study confirmed that FRA is a reasonable target for lung cancer.

On Target Laboratories, LLC has developed OTL38. Compared with some of the existing fluorescent imaging agents, OTL38 is associated with less auto-fluorescence due to its near-IR excitation wavelength and can be seen through blood and tissues up to 1.5 cm thickness. Thus, in this study, the investigator's goal has changed from the folate-FITC formulation to the OTL38 formulation. The fluorophore component of the drug is new, whereas the target and design of the study remain unchanged.

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

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:

• Adult patients over 18 years of age
• Patients presenting with a lung or pleural nodule or mass presumed to be resectable on pre- operative assessment
• Good operative candidate
• Subject capable of giving informed consent and participating in the process of consent.

Exclusion Criteria:

• Pregnant women as determined by urinary or serum beta hCG within 72 hours of surgery
• Patients with a history of anaphylactic reactions to OTL38
• Patients with a known allergy to Benadryl

• At-risk patient populations:

  • Homeless patients
  • Patients with drug or alcohol dependence
  • Children and neonates
  • Patients unable to participate in the consent process.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OTL38; Dosage calculated by weight of individual	Drug: OTL38; Infusion of OTL38 prior to surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability of the imaging system to detect the expression of the OTL38 in the nodule/mass (i.e tumor) and discern the uptake of the dye by the tumor.	Detected with imaging probe.	5 years
Microscopic examination and immunohistochemistry of tumor	Performed by a pathologist. This will allow investigators to compare pathology results with video images taken by imaging probe to calculate false positive (i.e., identification of non FRA-positive tumors) rates of OTL38.	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence rates of all AEs, treatment-emergent adverse events (TEAEs) and adverse device events (ADEs) from time of OTL38 administration through participants' first, post-operative appointment with surgeon.	5 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Sunil Singhal, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: November 2, 2015
• First Submitted That Met QC Criteria: November 9, 2015
• First Posted (Estimate): November 11, 2015

Study Record Updates

• Last Update Posted (Actual): June 28, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Multiple Pulmonary Nodules
• Other Study ID Numbers: 822153