E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
adenocarcinoma lung cancer |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Surgical Procedures, Operative [E04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025044 |
E.1.2 | Term | Lung cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To estimate the Sensitivity and False Positive rate of OTL38 for malignancy detection during Near Infrared Imaging (NIR). • To assess the safety and tolerability of single intravenous doses of OTL38. |
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E.2.2 | Secondary objectives of the trial |
Secondary • To assess the safety of the Fluorescence Imaging Systems for intraoperative imaging when used with OTL38. • To estimate the efficacy of OTL38 and NIR with respect to the identification of Clinically Significant Events (CSEs).
Exploratory • To compare the difference in detection rates of adenocarcinoma between OTL38 fluorescence vs frozen section assessment as determined by final pathology report. • To assess the Tumor to Background Ratios (TBR) in NIR systems capable of calculating TBR and their correlation to histological subtypes and clinical parameters. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion: 1. Male and Female patients 18 years of age and older 2. Confirmed diagnosis of adenocarcinoma lung cancer OR, 3. Have a primary diagnosis, or at high clinical suspicion, of lung nodule(s) warranting surgery based on CT and/or PET imaging 4. Who are scheduled to undergo endoscopic or thoracic surgery 5. 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 6. 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 7. 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 |
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E.4 | Principal exclusion criteria |
1. Previous exposure to OTL38 2. Known FR-negative lung nodules 3. Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the patient 4. History of anaphylactic reactions 5. History of allergy to any of the components of OTL38, including folic acid 6. Pregnancy, or positive pregnancy test 7. Clinically significant abnormalities on electrocardiogram (ECG) at screening. 8. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 9. Impaired renal function defined as eGFR< 50 mL/min/1.73m2 10. 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. 11. Received an investigational agent in another investigational drug or vaccine trial within 30 days prior to surgery 12. Known sensitivity to fluorescent light |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoints are the Sensitivity and False Positive rate of OTL38 for malignancy detection during Near Infrared Imaging (NIR). • 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). • 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). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary The secondary efficacy endpoint is proportion of patients with at least one CSE as a result of utilizing OTL-38 and Near Infrared Imaging. These include: 1. Identification of at least one pulmonary nodule identified with OTL-38 and Near Infrared Imaging (NIR) that was not identified by white light and finger palpation, OR 2. Identification of at least one synchronous lesion identified with OTL38 and NIR that was not identified by white light, OR 3. Identification of at least one positive cancer margin identified with OTL38 and NIR (in situ or back table) OR 4. Demonstration of at least one Intraoperative Challenge that could be resolved only by OTL-38 and NIR • Up/Down-Staging of a patient’s diagnosis • Operation scaling – increasing or decreasing scope of surgery. • Back table orientation - localization of a nodule or aspect of a nodule suspicious for cancer. Exploratory 1. The difference in detection rates of adenocarcinoma tissue samples (excluding lymph nodes) between OTL38 fluorescence at time of surgery vs. frozen section assessment as determined by final local pathology report. 2. To compare the proportion of all fluorescing lesions vs. the proportion of lesions expressing FRα+ and/or FRβ+ as determined by immunohistochemical analysis, excluding lymph nodes 3. Sensitivity and false positive rate estimated as described above for lymph nodes alone. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Netherlands |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |