Intraoperative Imaging of Pituitary Adenomas by OTL

August 2, 2019 updated by: Sunil Singhal, University of Pennsylvania

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Adult patients over 18 years of age
  2. Patients presenting with a pituitary nodule presumed to be resectable on pre-operative assessment
  3. Good operative candidate
  4. Subject capable of giving informed consent and participating in the process of consent.

Exclusion Criteria:

  1. Pregnant women as determined by urinary or serum beta human chorionic gonadotropin (hCG) within 72 hours of surgery
  2. Patients with a history of anaphylactic reactions to OTL38
  3. Patients with a known allergy to Benadryl
  4. Previous exposure to OTL38

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: OTL38
Dosage calculated by weight of individual
Drug: OTL38
Infusion of OTL38 prior to surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Detection of OTL38 in tumor tissue.
Time Frame: 60 months
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.
Time Frame: 60 months
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
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.
Time Frame: 60 months
60 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2015

Primary Completion (Actual)

August 3, 2018

Study Completion (Actual)

August 3, 2018

Study Registration Dates

First Submitted

December 4, 2015

First Submitted That Met QC Criteria

December 9, 2015

First Posted (Estimate)

December 14, 2015

Study Record Updates

Last Update Posted (Actual)

August 6, 2019

Last Update Submitted That Met QC Criteria

August 2, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 822782

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neoplasms

Clinical Trials on OTL38

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Georgia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe