Demeclocycline Fluorescence for Intraoperative Delineation Brain Tumors

NCT02740933 | Unknown Phase 1 DMC

• 1 other identifier: 15-280
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Brain Tumor

Keywords

Brain Tumor Surgery

Outcome Measures

Primary Outcomes (1)

• Detectable fluorescence in brain tumors by confocal microscopy after oral dosing of demeclocycline (Y/N).

  Detectable fluorescence via confocal microscopy

  2 years

Secondary Outcomes (1)

• Sensitivity And Specificity Of Demeclocycline-Enhanced Multimodal Confocal Microscopy of Excised Glioma Specimens

  2 years

Study Arms (1)

Demeclocycline

EXPERIMENTAL

All subjects will take Demeclocycline 300 mg po bid. Patients will be advised to take demeclocycline on an empty stomach, at least 1-2 hours before meals, and they will be warned that it can reduce the efficacy of oral contraceptives. The investigators will begin by treating subjects with 2 days of demeclocycline. The investigators will increase the numbers of days that subjects are exposed to demeclocycline in increments of 1 day until at least 80% of patients at a given dose have detectably fluorescent tumors, or participants reach 5 days of drug, whichever comes first.

Drug: Demeclocycline

Interventions

Demeclocycline DRUG

Also known as: Declomycin

Demeclocycline

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (13)

• 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.

  PMID: 19269895 BACKGROUND

• 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.

  PMID: 18667747 BACKGROUND

• 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.

  PMID: 21417701 BACKGROUND

• 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.

  PMID: 19687690 BACKGROUND

• 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. doi: 10.3171/jns.2003.99.3.0467.

  PMID: 12959431 BACKGROUND

• 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.

  PMID: 18425006 BACKGROUND

• 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.

  PMID: 24618801 BACKGROUND

• 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.

  PMID: 21868284 BACKGROUND

• 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.

  PMID: 24872922 BACKGROUND

• 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.

  PMID: 21761971 BACKGROUND

• 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.

  PMID: 22463044 BACKGROUND

• 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.

  PMID: 22882328 BACKGROUND

• 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.

  PMID: 25239672 BACKGROUND

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Demeclocycline

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• William T Curry, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

William T Curry, MD

CONTACT

617-726-3779

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: William T. Curry, MD

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: April 15, 2016
• Study Start: April 1, 2016
• Primary Completion: January 1, 2019
• Study Completion: January 1, 2021
• Last Updated: April 15, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)