Demeclocycline Fluorescence for Intraoperative Delineation Brain Tumors

Brain Tumor Clinical Trial

Official title:

Demeclocycline Fluorescence for Intraoperative Delineation Brain Tumors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02740933
• Other study ID #: 15-280
• Status: Not yet recruiting
• Phase: Phase 1
• First received: March 15, 2016
• Last updated: April 12, 2016
• Start date: April 2016
• Est. completion date: January 2021

Study information

• Verified date: April 2016
• Source: Massachusetts General Hospital
• Contact: William T Curry, MD
• Phone: 617-726-3779
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This research study is studying a drug called Demeclocycline that may help brain surgeons see tumors with a microscope during surgery.

Description:

This research study is a Feasibility Study, which is the first time investigators are examining this study intervention.The FDA (the U.S. Food and Drug Administration) has not approved Demeclocycline for your specific disease but it has been approved for other uses.

In this research study, the investigators would like to determine the lowest dose of Demeclocycline that will allow surgeons to detect tumor cells during surgery. These cells will be marked through a process called fluorescence, which will cause tumor cells to glow brightly on an image in comparison to its surroundings.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: January 2021
• Est. primary completion date: January 2019
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

• Participants must present with a gadolinium-enhancing brain lesion (or lesions) that are thought by the neuroradiologist and the neurosurgeon to be consistent with high-grade glioma. These may be newly diagnosed lesions or recurrent tumors.

• The patient must not be pregnant or nursing. Tetracycline (Demeclocycline, Doxycycline, Minocycline, Tetracycline, and Tigecycline) are classified as FDA pregnancy category D. Maternal ingestion of Tetracyclines during pregnancy may cause tooth discoloration, enamel defects, and other congenital anomalies. Tetracyclines are excreted in human breast milk; however, the extent of absorption of Tetracyclines by the breastfed infant is not known.

• Participants must have normal organ and marrow function as defined below:

• leukocytes = 3,000/mcL

• absolute neutrophil count = 1,500/mcL

• platelets = 100,000/mcL

• total bilirubin within normal institutional limits

• AST(SGOT)/ALT(SGPT) = 4 × institutional upper limit of normal

• creatinine < 2mg/dL

• Ability to understand and the willingness to sign a written informed consent document.

• Participants must be undergoing a surgical procedure with the intention of removing more tissue than what would be taken for a biopsy.

Exclusion Criteria:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Demeclocycline.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant and/or nursing women are excluded from this study because Demeclocycline is a known Teratogenic agent, pregnancy category D. It is known to be excreted in breast milk.

• Patients taking etinoid medications by mouth (such as Acitretin, Isotretinoin), Strontium Ranelate may not take Demeclocycline because of toxic interactions

• Patients taking any tetracycline class of drug (i.e. Minocycline, etc).

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumor

Intervention

Drug:
• Demeclocycline

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (13)

Laws ER, Parney IF, Huang W, Anderson F, Morris AM, Asher A, Lillehei KO, Bernstein M, Brem H, Sloan A, Berger MS, Chang S; Glioma Outcomes Investigators. Survival following surgery and prognostic factors for recently diagnosed malignant glioma: data from the Glioma Outcomes Project. J Neurosurg. 2003 Sep;99(3):467-73. — View Citation

Liu JT, Meza D, Sanai N. Trends in fluorescence image-guided surgery for gliomas. Neurosurgery. 2014 Jul;75(1):61-71. doi: 10.1227/NEU.0000000000000344. Review. — View Citation

McGirt MJ, Mukherjee D, Chaichana KL, Than KD, Weingart JD, Quinones-Hinojosa A. Association of surgically acquired motor and language deficits on overall survival after resection of glioblastoma multiforme. Neurosurgery. 2009 Sep;65(3):463-9; discussion 469-70. doi: 10.1227/01.NEU.0000349763.42238.E9. — View Citation

Pichlmeier U, Bink A, Schackert G, Stummer W; ALA Glioma Study Group. Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients. Neuro Oncol. 2008 Dec;10(6):1025-34. doi: 10.1215/15228517-2008-052. Epub 2008 Jul 30. — View Citation

Sanai N, Polley MY, McDermott MW, Parsa AT, Berger MS. An extent of resection threshold for newly diagnosed glioblastomas. J Neurosurg. 2011 Jul;115(1):3-8. doi: 10.3171/2011.2.JNS10998. Epub 2011 Mar 18. — View Citation

Sanai N, Snyder LA, Honea NJ, Coons SW, Eschbacher JM, Smith KA, Spetzler RF. Intraoperative confocal microscopy in the visualization of 5-aminolevulinic acid fluorescence in low-grade gliomas. J Neurosurg. 2011 Oct;115(4):740-8. doi: 10.3171/2011.6.JNS11252. Epub 2011 Jul 15. — View Citation

Senft C, Bink A, Franz K, Vatter H, Gasser T, Seifert V. Intraoperative MRI guidance and extent of resection in glioma surgery: a randomised, controlled trial. Lancet Oncol. 2011 Oct;12(11):997-1003. doi: 10.1016/S1470-2045(11)70196-6. Epub 2011 Aug 23. — View Citation

Snuderl M, Wirth D, Sheth SA, Bourne SK, Kwon CS, Ancukiewicz M, Curry WT, Frosch MP, Yaroslavsky AN. Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors. Brain Pathol. 2013 Jan;23(1):73-81. doi: 10.1111/j.1750-3639.2012.00626.x. Epub 2012 Aug 28. — View Citation

Stummer W, Reulen HJ, Meinel T, Pichlmeier U, Schumacher W, Tonn JC, Rohde V, Oppel F, Turowski B, Woiciechowsky C, Franz K, Pietsch T; ALA-Glioma Study Group. Extent of resection and survival in glioblastoma multiforme: identification of and adjustment for bias. Neurosurgery. 2008 Mar;62(3):564-76; discussion 564-76. doi: 10.1227/01.neu.0000317304.31579.17. — View Citation

Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, Hau P, Brandes AA, Gijtenbeek J, Marosi C, Vecht CJ, Mokhtari K, Wesseling P, Villa S, Eisenhauer E, Gorlia T, Weller M, Lacombe D, Cairncross JG, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groups; National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009 May;10(5):459-66. doi: 10.1016/S1470-2045(09)70025-7. Epub 2009 Mar 9. — View Citation

Wirth D, Snuderl M, Curry W, Yaroslavsky A. Comparative evaluation of methylene blue and demeclocycline for enhancing optical contrast of gliomas in optical images. J Biomed Opt. 2014 Sep;19(9):90504. doi: 10.1117/1.JBO.19.9.090504. — View Citation

Wirth D, Snuderl M, Sheth S, Kwon CS, Frosch MP, Curry W, Yaroslavsky AN. Identifying brain neoplasms using dye-enhanced multimodal confocal imaging. J Biomed Opt. 2012 Feb;17(2):026012. doi: 10.1117/1.JBO.17.2.026012. — View Citation

Zehri AH, Ramey W, Georges JF, Mooney MA, Martirosyan NL, Preul MC, Nakaji P. Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal systems, and future imaging modalities. Surg Neurol Int. 2014 Apr 28;5:60. doi: 10.4103/2152-7806.131638. eCollection 2014. Review. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detectable fluorescence in brain tumors by confocal microscopy after oral dosing of demeclocycline (Y/N).	Detectable fluorescence via confocal microscopy	2 years	No
Secondary	Sensitivity And Specificity Of Demeclocycline-Enhanced Multimodal Confocal Microscopy of Excised Glioma Specimens	We aim to measure the sensitivity and specificity with which tumors can be diagnosed accurately after satisfactory detection of fluorescence	2 years	No