Intraoperative Imaging of Pituitary Adenomas by OTL

NCT02629549 | Terminated Phase 1 DMC

• 1 other identifier: 822782
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neoplasms; Pituitary Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• 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

Study Arms (1)

OTL38

EXPERIMENTAL

Dosage calculated by weight of individual

Drug: OTL38

Interventions

OTL38 DRUG

Infusion of OTL38 prior to surgery

OTL38

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (17)

• Liu X, Ma S, Yao Y, Li G, Feng M, Deng K, Dai C, Cai F, Li Y, Zhang B, Wang R. Differential expression of folate receptor alpha in pituitary adenomas and its relationship to tumor behavior. Neurosurgery. 2012 May;70(5):1274-80; discussion 1280. doi: 10.1227/NEU.0b013e3182417e76.

  PMID: 22089756 BACKGROUND

• Evans CO, Yao C, Laborde D, Oyesiku NM. Folate receptor expression in pituitary adenomas cellular and molecular analysis. Vitam Horm. 2008;79:235-66. doi: 10.1016/S0083-6729(08)00408-1.

  PMID: 18804697 BACKGROUND

• Evans CO, Reddy P, Brat DJ, O'Neill EB, Craige B, Stevens VL, Oyesiku NM. Differential expression of folate receptor in pituitary adenomas. Cancer Res. 2003 Jul 15;63(14):4218-24.

  PMID: 12874029 BACKGROUND

• Feng Y, Shen J, Streaker ED, Lockwood M, Zhu Z, Low PS, Dimitrov DS. A folate receptor beta-specific human monoclonal antibody recognizes activated macrophage of rheumatoid patients and mediates antibody-dependent cell-mediated cytotoxicity. Arthritis Res Ther. 2011 Apr 8;13(2):R59. doi: 10.1186/ar3312.

  PMID: 21477314 BACKGROUND

• Hilgenbrink AR, Low PS. Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci. 2005 Oct;94(10):2135-46. doi: 10.1002/jps.20457.

  PMID: 16136558 BACKGROUND

• Kennedy MD, Jallad KN, Thompson DH, Ben-Amotz D, Low PS. Optical imaging of metastatic tumors using a folate-targeted fluorescent probe. J Biomed Opt. 2003 Oct;8(4):636-41. doi: 10.1117/1.1609453.

  PMID: 14563201 BACKGROUND

• Low PS, Antony AC. Folate receptor-targeted drugs for cancer and inflammatory diseases. Adv Drug Deliv Rev. 2004 Apr 29;56(8):1055-8. doi: 10.1016/j.addr.2004.02.003. No abstract available.

  PMID: 15094205 BACKGROUND

• Xia W, Low PS. Folate-targeted therapies for cancer. J Med Chem. 2010 Oct 14;53(19):6811-24. doi: 10.1021/jm100509v. No abstract available.

  PMID: 20666486 BACKGROUND

• Lu Y, Sega E, Leamon CP, Low PS. Folate receptor-targeted immunotherapy of cancer: mechanism and therapeutic potential. Adv Drug Deliv Rev. 2004 Apr 29;56(8):1161-76. doi: 10.1016/j.addr.2004.01.009.

  PMID: 15094213 BACKGROUND

• Lu Y, Xu LC, Parker N, Westrick E, Reddy JA, Vetzel M, Low PS, Leamon CP. Preclinical pharmacokinetics, tissue distribution, and antitumor activity of a folate-hapten conjugate-targeted immunotherapy in hapten-immunized mice. Mol Cancer Ther. 2006 Dec;5(12):3258-67. doi: 10.1158/1535-7163.MCT-06-0439.

  PMID: 17172429 BACKGROUND

• Paulos CM, Reddy JA, Leamon CP, Turk MJ, Low PS. Ligand binding and kinetics of folate receptor recycling in vivo: impact on receptor-mediated drug delivery. Mol Pharmacol. 2004 Dec;66(6):1406-14. doi: 10.1124/mol.104.003723. Epub 2004 Sep 15.

  PMID: 15371560 BACKGROUND

• Stephenson SM, Low PS, Lee RJ. Folate receptor-mediated targeting of liposomal drugs to cancer cells. Methods Enzymol. 2004;387:33-50. doi: 10.1016/S0076-6879(04)87003-4. No abstract available.

  PMID: 15172156 BACKGROUND

• Yang J, Chen H, Vlahov IR, Cheng JX, Low PS. Characterization of the pH of folate receptor-containing endosomes and the rate of hydrolysis of internalized acid-labile folate-drug conjugates. J Pharmacol Exp Ther. 2007 May;321(2):462-8. doi: 10.1124/jpet.106.117648. Epub 2007 Feb 8.

  PMID: 17289839 BACKGROUND

• Dorward NL. Endocrine outcomes in endoscopic pituitary surgery: a literature review. Acta Neurochir (Wien). 2010 Aug;152(8):1275-9. doi: 10.1007/s00701-010-0649-y. Epub 2010 May 10.

  PMID: 20454982 BACKGROUND

• Swearingen B. Update on pituitary surgery. J Clin Endocrinol Metab. 2012 Apr;97(4):1073-81. doi: 10.1210/jc.2011-3237. Epub 2012 Feb 15.

  PMID: 22337908 BACKGROUND

• Berkmann S, Schlaffer S, Nimsky C, Fahlbusch R, Buchfelder M. Follow-up and long-term outcome of nonfunctioning pituitary adenoma operated by transsphenoidal surgery with intraoperative high-field magnetic resonance imaging. Acta Neurochir (Wien). 2014 Dec;156(12):2233-43; discussion 2243. doi: 10.1007/s00701-014-2210-x. Epub 2014 Sep 2.

  PMID: 25174805 BACKGROUND

• Sylvester PT, Evans JA, Zipfel GJ, Chole RA, Uppaluri R, Haughey BH, Getz AE, Silverstein J, Rich KM, Kim AH, Dacey RG, Chicoine MR. Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas. Pituitary. 2015 Feb;18(1):72-85. doi: 10.1007/s11102-014-0560-2.

  PMID: 24599833 BACKGROUND

MeSH Terms

Conditions

Neoplasms; Pituitary Neoplasms

Interventions

Pafolacianine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Thoracic Surgery Research Laboratory

Study Record Dates

• First Submitted: December 4, 2015
• First Posted: December 14, 2015
• Study Start: October 1, 2015
• Primary Completion: August 3, 2018
• Study Completion: August 3, 2018
• Last Updated: August 6, 2019

Record last verified: 2019-08

Locations

US (1)