Ensayos clínicos

Inclusion Criteria:

• Patients must have a pathogenic variant in the NF2 gene (either in the germline or in two NF2-related tumors) OR a confirmed diagnosis of NF2 by fulfilling National Institute of Health (NIH) criteria or Manchester criteria.  The NIH criteria18 includes 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 criteria19 includes 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.
• Participants must have a target NF2-related tumor (VS, non-VS, meningioma, or ependymoma) with documented radiographic progression within the preceding 36 months of Master Study registration defined as either:
  • ≥ 20% increase in volume of enhancing tumor;
  • ≥ 2 mm increase in greatest linear dimension of enhancing tumor.
• Participants must have measurable disease, defined as:
  • VS, non-VS, or meningioma target lesions that can be accurately measured as ≥1 ml by volumetric MRI scan or in at least one dimension as ≥10 mm with conventional MRI scan. 
• Ependymoma target lesions measurable linearly. 
• Participant must have a target NF2-related tumor with the following qualities:
  • Not amenable to surgery due to patient refusal or due to high risk for surgical complications (e.g., damage to nerve function).
• Participant must be ≥ 12 years of age on Day 1 of treatment.
• Life expectancy of greater than 1 year.
• For participants 16 or older: Karnofsky performance status ≥ 70 or ECOG PS 0 or 1; for participants age 12 to < 16: Lansky scale ≥ 70.
• Ability to understand and the willingness to sign written informed consent and assent documents.
• Must have established relationship with primary care physician and provide contact information.

Exclusion Criteria:

• Participants who have had chemotherapy within a minimum of 4 weeks prior to Master Study registration (or a minimum of 5 half-lives and resolution to baseline of toxicities unless there are irreversible toxicities from prior drug that do not influence risk of next drug). 
• Participants who have received radiation to the target tumor within the last 3 years prior to Master study registration.
• Participants who are receiving any other investigational agents.
• Participants with target or non-target nervous system tumors that, in the opinion of the treating investigator, are likely to require active treatment (including surgery) within 6 months of registration to the Master Study.
• History of a different malignancy, unless:
  • have been disease-free for at least 2 years and are deemed by the treating investigator to be at low risk for recurrence of that malignancy; and/or
  • malignancy was breast or cervical cancer in situ, superficial bladder cancer or basal cell or squamous cell carcinoma of the skin, and malignancy has been treated. Patients who meet the above listed criteria and are only on preventative treatment will be deemed eligible.
• Pregnant women are excluded from this study because the experimental agents may have the potential for teratogenic or abortifacient effects.  Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these experimental agents, breastfeeding should be discontinued if the mother is treated.

Eligibility last updated 8/20/21.  Questions regarding updates should be directed to the study team contact.