NeoplasmsPhase 1NCT02629549
Intraoperative Imaging of Pituitary Adenomas by OTL
A Phase 1 study testing OTL38 in people with Neoplasms and Pituitary Neoplasms, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Pituitary Neoplasms
- What is being tested?
- OTL38
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to 3 Aug 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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.
Read the 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.
- Conditions
- Neoplasms, Pituitary Neoplasms
- Being tested
- OTL38
- Medical subject headings
- Neoplasms, Pituitary Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OTL38Drug
Infusion of OTL38 prior to surgery
| Study group | Role | What they receive |
|---|---|---|
| OTL38 | Experimental | Dosage calculated by weight of individual Receives: Drug: OTL38 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2015 (estimated)
- Study startOct 2015
- Primary completion3 Aug 2018
- Study completion3 Aug 2018
Why it stopped: Recruitment Fulfilled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (17)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sunil Singhal, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02629549
- Sponsor's protocol ID
- 822782
- Status last verified
- Aug 2019
- First submitted
- 4 Dec 2015
- Last updated
- 6 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22089756Evans 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.
PubMed 18804697Evans 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.
PubMed 12874029Feng 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.
PubMed 21477314Hilgenbrink 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.
PubMed 16136558Kennedy 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.
PubMed 14563201Low 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.
PubMed 15094205Xia 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.
PubMed 20666486Lu 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.
PubMed 15094213Lu 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.
PubMed 17172429Paulos 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.
PubMed 15371560Stephenson 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.
PubMed 15172156Yang 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.
PubMed 17289839Dorward 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.
PubMed 20454982Swearingen 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.
PubMed 22337908
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02629549
- Acronym / sponsor ID
- 822782
- Conditions
- Neoplasms, Pituitary Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment Fulfilled
- Enrolment
- 33 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- 3 Aug 2018 (actual)
- Study completion
- 3 Aug 2018 (actual)
- First posted
- 14 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| OTL38 | Experimental | Drug: OTL38Dosage calculated by weight of individual |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OTL38Infusion of OTL38 prior to surgery | Drug | OTL38 |
Primary outcome
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.
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.
1 secondary outcome
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
Results and safety
The study was stopped early (reason given: Recruitment Fulfilled). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2019.
- Background: PubMed 22089756Liu 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.
- Background: PubMed 18804697Evans 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.
- Background: PubMed 12874029Evans 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.
- Background: PubMed 21477314Feng 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.
- Background: PubMed 16136558Hilgenbrink 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.
- Background: PubMed 14563201Kennedy 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.
- Background: PubMed 15094205Low 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.
- Background: PubMed 20666486Xia 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.
- Background: PubMed 15094213Lu 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.
- Background: PubMed 17172429Lu 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.
- Background: PubMed 15371560Paulos 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.
- Background: PubMed 15172156Stephenson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing OTL38 in people with Neoplasms and Pituitary Neoplasms, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment Fulfilled). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detection of OTL38 in tumor tissue. (time frame: 60 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02629549, which also lists 17 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2019.