OTL38 for Intra-operative Imaging of Folate Receptor Positive Ovarian Cancer

Study Overview
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Brief Summary
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This is a phase 3, randomized, multi-center, single dose, open label, pivotal study in patients diagnosed with, or with high clinical suspicion of, ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery.

Detailed Description
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The Phase 3 study is to confirm the efficacy of OTL38 in combination with fluorescent light to detect additional Folate Receptor-positive (FR+) ovarian cancer lesions not detected by palpation and visualization under normal light in patients with FR+ ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Official Title
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A Phase 3, Randomized, Single Dose, Open-Label Study to Investigate the Safety and Efficacy of OTL38 Injection (OTL38) for Intra-operative Imaging of Folate Receptor Positive Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: OTL38
* Device: near infrared camera imaging system
* Procedure: laparotomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients 18 years of age and older Have a primary diagnosis, or at high clinical suspicion, of primary ovarian cancer (of epithelial type), planned for primary surgical cytoreduction, interval debulking, or have recurrent ovarian cancer surgery, and: Who are scheduled to undergo laparotomy for the debulking surgery OR Who are scheduled to undergo laparoscopy and pre-authorized to undergo laparotomy for the debulking surgery if cancer is detected on the laparoscopy 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 for participation in the study 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 FR-negative ovarian cancer Planned surgical debulking via laparoscopy or robotic surgery, with no intent of laparotomy. Patients with known ovarian cancer miliary disease determined preoperatively to be inoperable. Any medical condition that, in the opinion of the investigators, could potentially jeopardize the safety of the patient History of anaphylactic reactions History of allergy to any of the components of OTL38, including folic acid Pregnancy or positive pregnancy test Clinically significant abnormalities on electrocardiogram (ECG) 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 eGFR< 50 mL/min/1.73m2 Impaired liver function defined as values > 3x the upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin. Known Stage IV ovarian cancer with brain metastases Received an investigational agent in another clinical trial within 30 days prior to surgery Known sensitivity to fluorescent light

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: no fluorescent imaging<br>Patient injected with OTL38, but does not undergo fluorescent imaging | Drug: OTL38<br>* 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes<br>* Other names: OTL38 for Injection;Procedure: laparotomy<br>* primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery<br>|
| Experimental: near infrared imaging arm<br>Patient injected with OTL38 and undergoes near infrared imaging | Drug: OTL38<br>* 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes<br>* Other names: OTL38 for Injection;Device: near infrared camera imaging system<br>* Infrared imaging used to excite OTL38 for fluorescence<br>* Other names: Near IR imaging;Procedure: laparotomy<br>* primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Patient Level | Percentage of patients with at least one evaluable FR+ ovarian cancer lesion confirmed by central pathology (Standard of truth) that was detected using the combination of OTL38 and fluorescent light but not under normal light or palpation (Full Analysis Set) | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient False Positive Rate | False Positive Rate at the patient level (FPRp) will be a major secondary efficacy endpoint and is defined as the percentage of women who underwent both normal light and fluorescent light (Intent-to-Image Set) | 30 days |