Doxycycline in Cutaneous Schwannoma (NF2)

Trial Title: Doxycycline in Cutaneous Schwannoma (NF2)

NCT ID: NCT05521048

Condition: Neurofibromatosis Type 2

Conditions: Official terms:
Neurofibromatoses
Neurofibromatosis 1
Neurofibroma
Neurilemmoma
Neurofibromatosis 2
Doxycycline

Conditions: Keywords:
Cutaneous schwannoma
Doxycycline

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Doxycycline Injection [Doxy]
Description: Injections between 0.1 ml to 4 ml of 10mg/ml doxycycline hyclate will be administered to a maximum of three tumors per patient. The dose administered will be calculated based on tumor size, not to exceed the estimated volume of the tumor or a maximum of 4 ml. Injection of 1% lidocaine may be given pre-doxycycline to reduce injection pain.
Arm group label: Single Arm Open Label

Other name: Doxycycline Hyclate

Summary: In this research study the investigators want to learn more about an alternate, local treatment for skin schwannomas. Specifically, local doxycycline intra-tumoral injection will be performed as a potential treatment for NF2-related skin schwannomas, ultimately reducing the risks and costs associated with standard surgical removal of such skin tumors if successful.

Detailed description: Study Design: Interventional Clinical Trial, single-arm, open-label Estimated Enrollment: Up to 19 participants with NF2-associated cutaneous or subcutaneous schwannomas Aims: To demonstrate change in peripheral schwannoma size following direct injection into the tumor with doxycycline hyclate. Nineteen neurofibromatosis type 2-associated peripheral cutaneous or subcutaneous schwannomas between 0.5 cm and 4 cm in greatest diameter will be diagnosed clinically, photographed for documentation of location, and injected with between 0.1 ml to 4 ml of 10mg/ml doxycycline hyclate (Fresenius Kabi, Canton, MA). A maximum of three tumors per patient will be injected. The dose administered will be calculated based on tumor size, not to exceed the estimated volume of the tumor or a maximum of 4 ml. The tumor volume will be estimated by electronic caliper measure of the greatest tumor diameter (D). (V=4/3piR3 where R is the radius (R=D/2) is measured in millimeters and the dose calculated by Vmm3/1000 = injection volume in milliliters). Repeat measures will be made at 6-months and 1-year follow up (+/- 1 month) and documented with electronic calipers and photography. Injection of 1% lidocaine may be given pre-doxycycline to reduce injection pain. Outcome: The primary outcome will be longitudinal change in tumor maximal diameter measured at 6-months and 1-year compared to baseline defined by a change of 25%. Secondary endpoints include patient reports of paresthesia, pain, skin breakdown or discoloration. Exploratory endpoints will be the change in the sum of maximal diameters.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Patients must have a confirmed diagnosis of neurofibromatosis 2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria, or by detection of a causative mutation in the NF2 gene. The NIH criteria include presence of: - Bilateral vestibular schwannomas, OR - First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR - Two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity. The Manchester criteria include presence of: - Bilateral vestibular schwannomas, OR First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR - Two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity OR - Unilateral vestibular schwannoma AND any two of: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR - Multiple meningiomas (two or more) AND unilateral vestibular schwannoma OR - Any two of: schwannoma, glioma, neurofibroma, cataract. 2. Patients must have measurable disease, defined as at least one cutaneous/subcutaneous schwannoma with the following qualities: - Maximal tumor diameter > 0.5 cm to < 4.0 cm that can be accurately measured by electronic calipers - Up to a maximum of 3 tumors/subject may be injected - Not located on the face 3. Age ≥ 8 years on day 1 of treatment. 4. Life expectancy of greater than 1 year 5. Lansky/Karnofsky performance status ≥ 60 6. Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy 7. Any neurologic deficits must be stable for ≥1 week 8. Patient or parent/legal guardian must be able to provide signed informed consent and assent (as applicable for minors) Exclusion Criteria: 1. Allergy to doxycycline or tetracycline 2. Tumors located on the face or major motor nerves 3. Patients currently receiving medical anticancer therapies or who have received medical anticancer therapies within 4 weeks of the start of study drug (including chemotherapy and molecular targeted agents), as these may interfere with the study drug 4. Radiation therapy to a study target tumor within 1 year prior to enrollment, or any radiation therapy within 4 weeks prior to enrollment, as these may interfere with our ability to assess response to study drug 5. Prior treatment with any investigational drug within the preceding 4 weeks, as they may interfere with the study drug 6. Unstable or rapidly progressive disease, including patients who require glucocorticoids for symptomatic control of brain or spinal tumors, as this would represent a high risk for inability to comply with the study requirements 7. Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: - symptomatic congestive heart failure of New York heart Association Class III or IV - unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease - severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is 90% or less at rest on room air - active (acute or chronic) or uncontrolled severe infections liver disease, such as cirrhosis or severe hepatic impairment (Child-Pugh class C) 8. Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Adequate contraception (oral contraceptives, contraceptive implants, vaginal ring, or intrauterine devices (IUDs)) must be used at the time of injection but does not need to be carried out past the 1st month of observation. 9. History of significant noncompliance with follow-up that would jeopardize the study evaluation. 10. Patients unwilling to or unable to comply with the study protocol.

Gender: All

Minimum age: 8 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Massachusetts Eye and Ear

Address:
City: Boston
Zip: 02214
Country: United States

Status: Recruiting

Contact:
Last name: D. B. Welling, M.D., PhD

Phone: 617-573-3632

Phone ext: 3
Email: brad_welling@meei.harvard.edu

Contact backup:
Last name: Christopher Wood

Phone: 617-573-4075
Email: cgwood@meei.harvard.edu

Start date: September 19, 2022

Completion date: December 2024

Lead sponsor:
Agency: Massachusetts Eye and Ear Infirmary
Agency class: Other

Source: Massachusetts Eye and Ear Infirmary

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05521048