Demeclocycline Fluorescence for Intraoperative Delineation Brain Tumors

Phase 1

• Conditions: Brain Tumor
• Interventions: Drug: Demeclocycline

• Registration Number: NCT02740933
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

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

Detailed 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.

Study Timeline

• Study First Submitted: 2016-03-15
• Status Verified: 2016-04
• Study Start: 2016-04
• Study First Submitted QC: 2016-04-12
• Last Update Submitted: 2016-04-12
• Study First Posted: 2016-04-15
• Last Update Posted: 2016-04-15
• Primary Completion: 2019-01
• Study Completion: 2021-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Demeclocycline	Demeclocycline	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.

Primary Outcome Measures

Name	Time	Method
Detectable fluorescence in brain tumors by confocal microscopy after oral dosing of demeclocycline (Y/N).	2 years	Detectable fluorescence via confocal microscopy

Secondary Outcome Measures

Name	Time	Method
Sensitivity And Specificity Of Demeclocycline-Enhanced Multimodal Confocal Microscopy of Excised Glioma Specimens	2 years	We aim to measure the sensitivity and specificity with which tumors can be diagnosed accurately after satisfactory detection of fluorescence

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States