Hearing Outcomes Using Fractionated Proton Radiation Therapy for Vestibular Schwannoma

In this research study we are looking at another type of radiation called proton radiation which is known to spare surrounding normal tissues from radiation. The proton radiation will be delivered using fractionated stereotactic radiotherapy (FSRT) to improve localization of the small tumor target. Proton radiation delivers minimal radiation beyond the area of the tumor. This may reduce side effects that patients would normally experience with conventional radiation therapy. In this research study, we are looking to determine the effects of fractionated proton radiotherapy on long-term hearing preservation and controlling tumor growth.

Study Overview

• Status: Active, not recruiting
• Conditions: Vestibular Schwannoma; Acoustic Neuroma
• Intervention / Treatment: Radiation: Fractionated proton radiation; Drug: Losartan

Detailed Description

• Proton radiation will be delivered daily for approximately 5.5 weeks. Participants will be assessed weekly for any side effects they may be experiencing.
• Participants will have a follow-up visit 6 months after their last proton radiation treatment and then every year from the time of treatment completion for 5 years. The following tests and procedures will be performed at these visits: medical history, physical exam, MRI scan, comprehensive hearing tests and a questionnaire.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• MRI confirmed unilateral vestibular schwannoma within 8 weeks prior to study entry
• Measurable disease, defined as a lesion that can be accurately measured in at least one dimension
• No prior radiotherapy with dose delivered to structures in proximity to the internal acoustic canal is allowable
• Participants must have baseline "useful hearing" defined at the discretion of the treating physician in the irradiated ear
• 18 years of age or older
• Life expectancy of greater than 60 months
• Karnofsky performance status 60 or greater
• Diagnosis of neurofibromatosis 2 (NF2) is permitted
• Women of child-bearing potential and men must agree to use adequate contraception during the interval of irradiation
• Able to tolerate the supine position as required for the radiation treatment unit and able to tolerate rotation needed for treatment delivery
• Able to tolerate the standard immobilization device that typically utilizes a dental impression mouth piece and thus requires breathing through the nasal passage.
• Willing and able to comply with comprehensive audiologic testing, at baseline prior to radiation therapy, at 6 months from treatment completion, and at annual timepoints for 5 years after completion
• Baseline Systolic Blood Pressure (BP) > 100mm Hg. This is based on the average of two values - separate seated, resting measurements taken five minutes apart. BP does not need to be checked in both arms unless a reading is below 110 mm Hg, in which case the other arm can be checked as well. If BP is checked in both arms, the higher value is deemed accurate for calculating the average.

Exclusion Criteria:

• Participants who have had prior radiotherapy, with dose delivered to structures in proximity to the internal acoustic canal (IAC).
• Participants with tumors (or residual tumor after surgery) measuring > 3cm in greatest dimension
• Participants may not be receiving any other study agents
• History of adverse reaction to radiotherapy
• Participants may not already be on losartan, other angiotensin II type I receptor blocker (ARB), or on an angiotensin-converting enzyme (ACE) inhibitor prior to enrollment of this study.
• Participants receiving any medications or substances that are known to cause ototoxicity are ineligible
• 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 women
• Individuals with a history of malignancy are ineligible except for the following circumstances. Individuals with a history of malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be a low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell squamous cell carcinoma of the skin.
• HIV-positive individuals on combination antiretroviral therapy
• Patients with co-existing major ear disease, such as chronic otitis, Menieres disease, or otosclerosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fractionated Proton Radiation; Single arm study, delivering fractionated radiation with a technique (proton therapy) that may be associated with reduced side effects	Radiation: Fractionated proton radiation; Given daily for approximately 5.5 weeks; Drug: Losartan; 25mg or 50mg daily, oral administration, for approximately 6 months.; Other Names: Cozaar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of long-term hearing effects	Characterization of long-term hearing effects of fractionated proton therapy in patients with vestibular schwannomas.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control rate after fractionated proton radiation		5 years
Delineation of dosimetric parameters after fractionated proton radiation	The distribution of dosimetric parameters will be summarized, and their correlation to clinical outcomes, including hearing loss, will be explored.	5 years
Incidence of second tumors after fractionated proton radiation		5 years
Toxicity profile of Losartan given concurrently with proton radiation	Toxicities associated with losartan before, during and after proton radiation will be summarized by grade according to CTCAE 4.0. The losartan cohort of 10 participants will provide 90% confidence interval of maximal width +/-27% based on the exact binomial distribution.	5 years
Impact of Losartan on hearing preservation		5 years
Impact of Losartan on circulating biomarkers		5 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Helen A. Shih, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Saraf A, Pike LRG, Franck KH, Horick NK, Yeap BY, Fullerton BC, Wang IS, Abazeed ME, McKenna MJ, Mehan WA, Plotkin SR, Loeffler JS, Shih HA. Fractionated Proton Radiation Therapy and Hearing Preservation for Vestibular Schwannoma: Preliminary Analysis of a Prospective Phase 2 Clinical Trial. Neurosurgery. 2022 May 1;90(5):506-514. doi: 10.1227/neu.0000000000001869.

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2011
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: September 9, 2010
• First Submitted That Met QC Criteria: September 10, 2010
• First Posted (Estimated): September 13, 2010

Study Record Updates

• Last Update Posted (Actual): March 26, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: radiation; fractionated proton radiation
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Otorhinolaryngologic Neoplasms; Otorhinolaryngologic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Ear Diseases; Nervous System Neoplasms; Cranial Nerve Diseases; Neuroendocrine Tumors; Nerve Sheath Neoplasms; Peripheral Nervous System Neoplasms; Cranial Nerve Neoplasms; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Neuroma; Neurilemmoma; Neuroma, Acoustic; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Losartan
• Other Study ID Numbers: 10-218

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No