OTL38 Injection for Intraoperative Imaging of Folate Rece... | NCT02872701

Status Module

Name	Class
Medelis Inc.	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Patients Receiving OTL38	Experimental	All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging.	Drug: OTL38 for Injection Device: Near infrared camera imaging system Procedure: Endoscopic or Thoracic Surgery

Interventions

Name	Type	Description	Arm Group Labels	Other Names
OTL38 for Injection	Drug	Folate analog ligand conjugated with an indole cyanine-like green dye as a solution in vials containing 3 mL at 2 mg/mL	Patients Receiving OTL38

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Sensitivity or True Positive Rate (TPR)	Sensitivity or True Positive Rate (TPR) for OTL38 in combination with fluorescent light, defined as the proportion of fluorescent light positive tissue samples (nodule, synchronous lesion, and margin but excluding lymph nodes) that are histologically confirmed to be FR+ and lung cancer by central pathology relative to the total number of tissue samples confirmed to be FR+ and lung cancer by central pathology. Sensitivity = (True Positive)/(True Positive +False Negative)	1 day
False Positive Rate (FPR)	False positive rate (FPR) for OTL38 in combination with fluorescent light, for the purpose of this protocol, will be calculated as 1 - the Positive Predictive Value (PPV) and is defined as the proportion of fluorescent light positive tissue samples removed (nodule, synchronous lesion, and margin but excluding lymph nodes) that are histologically confirmed to be non-cancerous, or if cancerous, not FR+ and lung cancer, by central pathology relative to the total number of tissue samples removed with fluorescent light imaging. False Positive Rate = (False Positives) / (True Positives + False Positives)	1 day

Secondary Outcomes

Measure	Description	Time Frame
Proportion of Patients With at Least 1 Clinically Significant Event (CSE)	Proportion of patients with at least 1 Clinically Significant Event (CSE as a result of utilizing OLT-38 and Near Infrared Imaging	1 day
Positive Margin Identification

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and Female patients 18 years of age and older
Confirmed diagnosis of adenocarcinoma lung cancer OR,
Have a primary diagnosis, or at high clinical suspicion, of lung nodule(s) warranting surgery based on CT and/or PET imaging
Who are scheduled to undergo endoscopic or thoracic surgery surgery
A negative serum pregnancy test at Screening followed by a negative urine pregnancy test on the day of surgery or day of admission for female patients of childbearing potential
Female patients 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
Known Folate Receptor-negative lung nodules
Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the patient
History of anaphylactic reactions or severe allergies
History of allergy to any of the components of OTL38, including folic acid
Pregnancy, or positive pregnancy test
Clinically significant abnormalities on electrocardiogram (ECG) at screening.
Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
Impaired renal function defined as epidermal growth factor receptor (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 total bilirubin.
Received an investigational agent in another investigational drug or vaccine trial within 30 days prior to surgery
Known sensitivity to fluorescent light

Name	Affiliation	Role
Sunil Singhal, MD	University of Pennsylvania	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Beth Israel Deaconess Medical Center		Boston	Massachusetts	02215	United States
Cleveland Clinic

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Patients Receiving OTL38	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 Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 14, 2018	Jan 13, 2023

Arm/Group Information

ID	Title	Description
BG000	Patients Receiving OTL38	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 Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery

Units	Counts
Participants	BG000100

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000
Between 18 and 65 years	BG00028
>=65 years	BG000

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00067.4± 9.35

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00068
Male	BG00032

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001
Not Hispanic or Latino	BG00098

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001
Asian	BG0007

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Netherlands

Title	Measurements
	BG00010

United States

Title	Measurements
	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Sensitivity or True Positive Rate (TPR)

Sensitivity or True Positive Rate (TPR) for OTL38 in combination with fluorescent light, defined as the proportion of fluorescent light positive tissue samples (nodule, synchronous lesion, and margin but excluding lymph nodes) that are histologically confirmed to be FR+ and lung cancer by central pathology relative to the total number of tissue samples confirmed to be FR+ and lung cancer by central pathology.

Sensitivity = (True Positive)/(True Positive +False Negative)

The FAS for the analysis of the two co-primary endpoints, sensitivity and FPR, included patients exposed to OTL38 who:

Were evaluated under both normal light and fluorescent light imaging, and
Had central pathology and histology confirmation (positive for FR+ Lung Cancer) for at least one tissue sample detected under normal light or fluorescent light imaging

Posted

Number

95% Confidence Interval

proportion of lesions

1 day

Lesions

ID	Title	Description
OG000	Patients Receiving OTL38	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 Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery

Units	Counts
Participants	OG00075
Lesions	OG000107

Title

Denominators

Categories

Title	Measurements
	OG0000.854(0.74 to 0.92)

Primary

False Positive Rate (FPR)

False positive rate (FPR) for OTL38 in combination with fluorescent light, for the purpose of this protocol, will be calculated as 1 - the Positive Predictive Value (PPV) and is defined as the proportion of fluorescent light positive tissue samples removed (nodule, synchronous lesion, and margin but excluding lymph nodes) that are histologically confirmed to be non-cancerous, or if cancerous, not FR+ and lung cancer, by central pathology relative to the total number of tissue samples removed with fluorescent light imaging. False Positive Rate = (False Positives) / (True Positives + False Positives)

The FAS for the analysis of the two co-primary endpoints, sensitivity and FPR, included patients exposed to OTL38 who:

Were evaluated under both normal light and fluorescent light imaging, and
Had central pathology and histology confirmation (positive for FR+ Lung Cancer) for at least one tissue sample detected under normal light or fluorescent light imaging

Posted

Number

95% Confidence Interval

proportion of lesions

1 day

Lesions

ID	Title	Description
OG000	Patients Receiving OTL38	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 Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery

Secondary

Proportion of Patients With at Least 1 Clinically Significant Event (CSE)

Proportion of patients with at least 1 Clinically Significant Event (CSE as a result of utilizing OLT-38 and Near Infrared Imaging

The FAS for the analysis of the two co-primary endpoints, sensitivity and FPR, included patients exposed to OTL38 who:

Were evaluated under both normal light and fluorescent light imaging, and
Had central pathology and histology confirmation (positive for FR+ Lung Cancer) for at least one tissue sample detected under normal light or fluorescent light imaging

Posted

Number

95% Confidence Interval

proportion of participants

1 day

ID	Title	Description
OG000	Patients Receiving OTL38	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 Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery

Units	Counts
Participants	OG000

Secondary

Positive Margin Identification

Number of patients where at least one positive margin (fluorescent cancerous cells within 5 mm of the staple line) is identified with only OTL-38 and NIR

The FAS for the analysis of the two co-primary endpoints, sensitivity and FPR, included patients exposed to OTL38 who:

Were evaluated under both normal light and fluorescent light imaging, and
Had central pathology and histology confirmation (positive for FR+ Lung Cancer) for at least one tissue sample detected under normal light or fluorescent light imaging

Posted

Count of Participants

Participants

1 day

ID	Title	Description
OG000	Patients Receiving OTL38	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 Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery

Units	Counts
Participants	OG000

Secondary

Synchronous Lesion Identification

Number of patients where at least one synchronous lesions is identified only with OTL-38 and NIR

The FAS for the analysis of the two co-primary endpoints, sensitivity and FPR, included patients exposed to OTL38 who:

Were evaluated under both normal light and fluorescent light imaging, and
Had central pathology and histology confirmation (positive for FR+ Lung Cancer) for at least one tissue sample detected under normal light or fluorescent light imaging

Posted

Count of Participants

Participants

1 day

ID	Title	Description
OG000	Patients Receiving OTL38	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 Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery

Units	Counts
Participants	OG000

Secondary

Pulmonary Nodule Identification

Number of pulmonary nodules identified with OTL-38 and Near Infrared Imaging (NIR) that could not otherwise be identified by white light and palpation.

The FAS for the analysis of the two co-primary endpoints, sensitivity and FPR, included patients exposed to OTL38 who:

Were evaluated under both normal light and fluorescent light imaging, and
Had central pathology and histology confirmation (positive for FR+ Lung Cancer) for at least one tissue sample detected under normal light or fluorescent light imaging

Posted

Number

number of pulmonary nodules

1 day

ID	Title	Description
OG000	Patients Receiving OTL38	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 Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Patients Receiving OTL38	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 Endoscopic or Thoracic Surgery: Endoscopic or Thoracic Surgery	0	100	14	100	94	100

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Haemothorax	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0002 events2 affected100 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0002 events2 affected100 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0002 events2 affected100 at risk
Chylothorax	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected100 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected100 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected100 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected100 at risk
Pneumonia	Infections and infestations	Non-systematic Assessment	EG0002 events2 affected100 at risk
Hip fracture	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0001 events1 affected100 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0001 events1 affected100 at risk
Small intestinal obstruction	Gastrointestinal disorders	Non-systematic Assessment	EG0002 events1 affected100 at risk
Arterial haemorrhage	Vascular disorders	Non-systematic Assessment	EG0001 events1 affected100 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Procedural pain	Injury, poisoning and procedural complications	Non-systematic Assessment	EG00050 events50 affected100 at risk
Incision site pain	Injury, poisoning and procedural complications	Non-systematic Assessment	EG00020 events20 affected100 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00029 events29 affected100 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00017 events17 affected100 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00017 events17 affected100 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00013 events13 affected100 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0007 events7 affected100 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0006 events6 affected100 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0006 events6 affected100 at risk
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG00033 events33 affected100 at risk
Vomiting	Gastrointestinal disorders	Non-systematic Assessment	EG00017 events17 affected100 at risk
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG00010 events10 affected100 at risk
Chest pain	General disorders	Non-systematic Assessment	EG00012 events12 affected100 at risk
Fatigue	General disorders	Non-systematic Assessment	EG00010 events10 affected100 at risk
Pyrexia	General disorders	Non-systematic Assessment	EG0006 events6 affected100 at risk
Respiratory complication associated with device	General disorders	Non-systematic Assessment	EG0006 events6 affected100 at risk
Hypertension	Vascular disorders	Non-systematic Assessment	EG00011 events11 affected100 at risk
Hypotension	Vascular disorders	Non-systematic Assessment	EG00011 events11 affected100 at risk
Atrial fibrillation	Cardiac disorders	Non-systematic Assessment	EG0008 events8 affected100 at risk
Tachycardia	Cardiac disorders	Non-systematic Assessment	EG0005 events5 affected100 at risk
Dizziness	Nervous system disorders	Non-systematic Assessment	EG0007 events7 affected100 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0006 events6 affected100 at risk
Pneumonia	Infections and infestations	Non-systematic Assessment	EG0007 events7 affected100 at risk
Pruritus	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0005 events5 affected100 at risk
Subcutaneous emphysema	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0005 events5 affected100 at risk
Hypokalaemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0005 events5 affected100 at risk
Urinary retention	Renal and urinary disorders	Non-systematic Assessment	EG0005 events5 affected100 at risk

ID	Term
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
C000720187	Pafolacianine
D007267	Injections
D004724	Endoscopy
D019616	Thoracic Surgical Procedures

ID	Term
D004333	Drug Administration Routes
D004358	Drug Therapy
D013812	Therapeutics
D003949	Diagnostic Techniques, Surgical
D019937	Diagnostic Techniques and Procedures
D003933	Diagnosis
D019060	Minimally Invasive Surgical Procedures
D013514	Surgical Procedures, Operative