Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Axitinib in Patients With Neurofibromatosis Type 2 and Progressive Vestibular Schwannomas|
- Radiographic tumor response (i.e. maximum tumor shrinkage) [ Time Frame: Within first 12 months of treatment, or until radiographic progression or unacceptable toxicity. ]
Radiographic response: for study purposes, a 20% or greater reduction in tumor volume in any of the target tumors will constitute a partial response (PR). Complete disappearance of any of the target tumors will constitute a complete response (CR).
MRI of the brain and spine (in patients with spinal tumors with medically relevant or symptomatic lesions) with 3D tumor volumetrics will be performed every 3 months.
If an objective response, defined as a 20% reduction in tumor volume compared to baseline is observed in any target tumor or stable disease in all target tumors (i.e. less than 20% increase in size), Axitinib will be continued. Therapy will be discontinued if the primary target tumor enlarges by 20%.
- Audiologic response [ Time Frame: Within first 12 months of treatment, or until radiographic progression or unacceptable toxicity ]
Audiologic response: improvement in speech discrimination score (SDS), defined as an improvement in the score above the 95% critical difference threshold, compared to baseline audiogram at initiation of treatment. Audiologic worsening: decrease in SDS score below the 95% critical difference threshold, compared to baseline audiogram at initiation of treatment.
Patients with vestibular schwannomas will receive baseline audiograms within 28 days before enrollment and subsequent audiograms at the time of each MRI.
Audiologic responses will be determined, but will not be used as primary response criteria.
|Study Start Date:||April 2014|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
5 mg axitinib orally twice daily, with increase to 7 mg orally twice daily and 10 mg orally twice daily after 2 and 4 weeks, respectively, provided no adverse reactions (i.e., not exceeding grade 2 toxicities) and normotensive and not receiving antihypertension medications. Axitinib will be given continuously in 28-day cycles until disease progression or unacceptable toxicity.
Other Name: Inlyta
NF2 is a condition that mainly affects the skin and nervous system. It causes non-cancerous tumors to grow on the nerves around a person's body. Some signs of NF2 include a gradual loss of hearing and tumors growing on the skin, the brain and the spinal cord, which can lead to complications.
AXITINIB is an oral drug (taken by mouth) that is approved by the United States Food and Drug Administration (FDA) for the treatment of other types of tumors. However, in this research study, AXITINIB is considered investigational because it is not approved by the FDA for treatment of NF2. Much is known regarding how well it is tolerated (handled), but investigators do not know if it is effective in treating NF2.
This research study will test whether AXITINIB may shrink tumors commonly found in patients with NF2 or stop them from growing. This will help to decide if AXITINIB should be used to treat NF2 patients in the future. AXITINIB is a drug that has been used to treat various forms of cancer. It has not been studied for the treatment of tumors in NF2 patients. Investigators have selected AXITINIB for this clinical trial in patients with NF2 and NF2-related tumors because a very similar drug, bevacizumab, can shrink Vestibular Schwannomas (VS) in some NF2 patients.
Pfizer, Inc., the manufacturer of the study drug, AXITINIB, will provide the AXITINIB being used in this study.
Primary Objective: To estimate the objective volumetric response rates to axitinib in adult NF2 patients with VS.
Secondary Objectives: To assess the toxicity of axitinib given daily in patients with NF2 and to examine the association of objective measures of response on MRI, i.e. volumetric tumor analysis with clinical measures of response, i.e. (audiogram), as well as quality of life assessments (NFTI-QOL). In addition, response in non-VS tumors, such as other schwannomas and meningiomas, may be explored.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02129647
|Contact: Matthias A Karajannis, MDemail@example.com|
|United States, New York|
|NYU Langone Medical Center||Recruiting|
|New York, New York, United States, 10016|
|Contact: Matthias Karajannis, MD 212-263-8400 firstname.lastname@example.org|
|Principal Investigator: Matthias A Karajannis, MD, MS|
|Sub-Investigator: Jeffrey Allen, MD|
|Sub-Investigator: Katharine McNeill, MD|
|Principal Investigator:||Matthias A Karajannis, MD, MS||NYU Langone Medical Center|