Intraoperative Imaging of Pituitary Adenomas by OTL

Study Overview
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Brief Summary
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The primary end-point of the study is to determine the specificity and sensitivity of OTL38 in identifying pituitary adenomas when excited by an imaging probe. The investigators intend to enroll 50 patients in this study. The study is focusing on patients presenting with suspected pituitary adenomas who are considered to be good surgical candidates.

Detailed Description
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Pituitary adenomas have an estimated prevalence in the population of approximately 10%, and although they are predominantly benign tumors, they can cause significant disability from mass effect (visual field deficits and cranial nerve deficits) and from hypersecretory syndromes (Cushing's disease, acromegaly, hyperprolactinemia). Approximately 30% of all pituitary adenomas are nonfunctioning or endocrinologically silent, and despite the lack of hormonal overexpression they represent the great majority of patients of who undergo surgery given the threat of apoplexy and compression of adjacent neural structures. Surgical resection via transsphenoidal surgery remains the primary treatment modality for almost all pituitary adenomas except prolactinomas. Residual tumor, however, is quite common after surgical resection and is seen in up to 20% of surgical cases. By ensuring a negative margin through imaging during surgery, it would be possible to minimize the need for postoperative radiation therapy and/or radiosurgery and subsequent surgery as well. Gross total resection (GTR) of a pituitary adenoma is theoretically simple but practically difficult given the intimate association of the pituitary gland with critical neurovascular structures including the internal carotid artery, optic nerves, cavernous sinus contents and adjacent frontal lobe and third ventricle. In a recent meta-analysis, functioning pituitary adenoma (Cushing's disease, prolactinoma, acromegaly) was demonstrated to have a gross total resection rate of only 78% (n=664). In another review, tabulated through multiple studies, demonstrated that for nonfunctioning pituitary adenoma, gross total resection rate ranged from 66 to 93% (n=778). Moreover, a comparison of endoscopic and microscopic removal of pituitary adenoma found the gross total resection rate was 66% using endoscopic pituitary techniques. In this context of limited ability to achieve GTR, intraoperative MRI was introduced for assessment of the degree of resection for pituitary adenoma. The intraoperative MRI is expensive, cumbersome, and impractical. A simpler means of determining the degree of resection is greatly needed in the field of brain surgery, and specifically pituitary surgery. Pituitary adenomas are the ideal disease to investigate intra-operative imaging. Multiple studies have demonstrated that nonfunctioning pituitary adenomas express folate receptor alpha (FRα), 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 2-3 hours. Tumor cells that over express FRα will retain folate and any fluorescent labeled folate conjugate (such as OTL38) and internalize this.

Official Title
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A Phase 1, Single Dose, Open-Label Study to Investigate the Safety and Efficacy of OTL38 Injection for Intraoperative Imaging of Folate Receptor-alpha Positive Pituitary Adenoma

Conditions
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Neoplasms, Pituitary Neoplasms

Intervention / Treatment
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* Drug: OTL38


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients over 18 years of age Patients presenting with a pituitary nodule 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 human chorionic gonadotropin (hCG) within 72 hours of surgery Patients with a history of anaphylactic reactions to OTL38 Patients with a known allergy to Benadryl Previous exposure to OTL38

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OTL38<br>Dosage calculated by weight of individual | Drug: OTL38<br>* Infusion of OTL38 prior to surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of OTL38 in tumor tissue. | The detection of OTL38 uptake by tumor tissue will be made with the use of an imaging system that detects the presence of dye in tissue. | 60 months | 
| Evaluate the ability of OTL38 to discern between tumorous tissue and normal, neural tissue. | Specificity and sensitivity of OTL38 will be calculated through the comparison of the video images gathered from the imaging system and the final pathology results from the surgical procedure. | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rates of all adverse events, treatment-emergent adverse events and adverse device events from time of OTL38 administration through participants' first, post-operative appointment with surgeon. |  | 60 months |