Lung Cancer, Lung Neoplasms
Conditions
Keywords
Intraoperative Imaging
Brief summary
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.
Interventions
Folate analog ligand conjugated with an indole cyanine-like green dye as a solution in vials containing 3 mL at 2 mg/mL
Near infrared camera imaging system
Sponsors
Clinipace Worldwide
On Target Laboratories, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Significant Events (CSE) | 1 day | 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. |
| Localization of Primary Nodule | 1 day | 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 |
| Identification of Cancerous Synchronous Lesions | 1 day | The proportion of FAS subjects with one or more NIR fluorescence positive cancerous synchronous lesions not detected under normal light and/or palpation |
| Positive Resection Margins | 1 day | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sensitivity for Cancerous Primary Nodules and Synchronous Lesions in FAS Subjects | 1 day | 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. |
| False Positive Rate for Cancerous Primary Nodules and Synchronous Lesions in FAS Subjects | 1 day | 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 |
Countries
United States
Participant flow
Pre-assignment details
1 subject dosed and withdrawal by subject prior to surgery
Participants by arm
| Arm | Count |
|---|---|
| Near-Infrared Imaging Group All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging.
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
Near infrared camera imaging system: Near infrared camera imaging system | 100 |
| No Imaging Group All patients in this arm will receive OTL38 for injection but will not receive intraoperative imaging.
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 | 11 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Near-Infrared Imaging Group | No Imaging Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 64 Participants | 6 Participants | 70 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 5 Participants | 41 Participants |
| Age, Continuous | 66 years STANDARD_DEVIATION 9.68 | 64 years STANDARD_DEVIATION 9.88 | 65.9 years STANDARD_DEVIATION 9.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 99 Participants | 11 Participants | 110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 88 Participants | 8 Participants | 96 Participants |
| Region of Enrollment United States | 100 participants | 11 participants | 111 participants |
| Sex: Female, Male Female | 61 Participants | 9 Participants | 70 Participants |
| Sex: Female, Male Male | 39 Participants | 2 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 0 / 11 |
| other Total, other adverse events | 98 / 100 | 11 / 11 |
| serious Total, serious adverse events | 7 / 100 | 2 / 11 |
Outcome results
Primary
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.
Time frame: 1 day
Population: Full Analysis Set (FAS): The FAS for the primary analysis of the primary efficacy endpoint will include subjects exposed to OTL38 and randomized to undergo fluorescent imaging (OTL38+Imaging) who:~• Were evaluated under both normal light/palpation and NIR fluorescent light imaging
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | Clinically Significant Events (CSE) | .530 proportion of participants |
Primary
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
Time frame: 1 day
Population: Full Analysis Set (FAS): The FAS for the primary analysis of the primary efficacy endpoint will include subjects exposed to OTL38 and randomized to undergo fluorescent imaging (OTL38+Imaging) who:~• Were evaluated under both normal light/palpation and NIR fluorescent light imaging
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | Identification of Cancerous Synchronous Lesions | .080 proportion of participants |
Primary
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
Time frame: 1 day
Population: Full Analysis Set (FAS): The FAS for the primary analysis of the primary efficacy endpoint will include subjects exposed to OTL38 and randomized to undergo fluorescent imaging (OTL38+Imaging) who:~• Were evaluated under both normal light/palpation and NIR fluorescent light imaging
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | Localization of Primary Nodule | .190 proportion of participants |
Primary
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
Time frame: 1 day
Population: Full Analysis Set (FAS): The FAS for the primary analysis of the primary efficacy endpoint will include subjects exposed to OTL38 and randomized to undergo fluorescent imaging (OTL38+Imaging) who:~• Were evaluated under both normal light/palpation and NIR fluorescent light imaging
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | Positive Resection Margins | .380 proportion of participants |
Secondary
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
Time frame: 1 day
Population: Total number of Subjects with Evaluated Tissues
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | False Positive Rate for Cancerous Primary Nodules and Synchronous Lesions in FAS Subjects | .258 proportion of lesions |
Secondary
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.
Time frame: 1 day
Population: Total number of Subjects with Evaluated Tissues
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Full Analysis Set (FAS) | Sensitivity for Cancerous Primary Nodules and Synchronous Lesions in FAS Subjects | .765 proportion of lesions |