Study of RAD001 for Treatment of NF2-related Vestibular Schwannoma

NCT01345136 | Terminated Phase 2 DMC

• 1 other identifier: 13-001492
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine if RAD001 treatment will shrink or slow the growth of the vestibular schwannoma(s) in Neurofibromatosis 2 (NF2) patients. Secondary objectives include determining if RAD001 treatment will improve hearing ability in NF2 patients. RAD001 is an oral drug that is approved by Food and Drug Administration (FDA) for other types of tumors, it is not approved by the FDA for treatment of NF2 related tumors.

Conditions

Neurofibromatosis Type 2; Neuroma, Acoustic

Keywords

Neurofibromatosis Type 2; Vestibular schwannoma; Hearing

Outcome Measures

Primary Outcomes (1)

• Vestibular schwannoma volume

  Determine the effect of RAD001 on change in vestibular schwannoma volume (mm3) by MRI from baseline to 1 year.

  1 year (12 months)

Secondary Outcomes (2)

• Hearing

  1 year (12 months)

• Number of adverse events

  1 year, 1 month (13 months)

Study Arms (1)

RAD001 Treatment

EXPERIMENTAL

All subjects will be given RAD001 for 1 year (12 months).

Drug: RAD001, everolimus

Interventions

RAD001, everolimus DRUG

Adults: 10 mg p.o. daily dose, age 16 - 17: 3.0 mg/m2 p.o. daily

Also known as: Everolimus, Afinitor

RAD001 Treatment

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of NF2 by National Institutes of Health (NIH) criteria
• Age ≥ 16 years
• Progressive VS growth during the previous 12 months.
• WHO performance status \> or = 2
• Adequate bone marrow, liver and renal function.
• For women of childbearing potential, no pregnancy or breast-feeding
• Willingness and ability to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
• Willingness to provide informed consent

You may not qualify if:

• Inability to tolerate periodic MRI scans or gadolinium contrast.
• Inability to tolerate periodic audiologic testing or to understand a language with established scoring for word recognition testing.
• Inability to adequately perform volumetric measurement of at least 1 target lesionNote: Patients with cochlear or auditory brainstem implants may participate if a target lesion can be accurately assessed.
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 4 weeks of the start of study drug.
• Immunization with attenuated live vaccines within one week of study entry or during study period.
• Presence of a fungal infection requiring systemic antifungal treatment at enrollment
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
• Patients who have any severe and/or uncontrolled medical conditions.
• Patients with a known hypersensitivity to everolimus or other types of rapamycin or to its excipients.
• Patients unwilling to or unable to comply with the protocol

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

University of California Los Angeles

Los Angeles, California, 90095-7286, United States

Location

Related Publications (3)

• Giovannini M, Bonne NX, Vitte J, Chareyre F, Tanaka K, Adams R, Fisher LM, Valeyrie-Allanore L, Wolkenstein P, Goutagny S, Kalamarides M. mTORC1 inhibition delays growth of neurofibromatosis type 2 schwannoma. Neuro Oncol. 2014 Apr;16(4):493-504. doi: 10.1093/neuonc/not242. Epub 2014 Jan 10.

  PMID: 24414536 BACKGROUND

• Goutagny S, Raymond E, Esposito-Farese M, Trunet S, Mawrin C, Bernardeschi D, Larroque B, Sterkers O, Giovannini M, Kalamarides M. Phase II study of mTORC1 inhibition by everolimus in neurofibromatosis type 2 patients with growing vestibular schwannomas. J Neurooncol. 2015 Apr;122(2):313-20. doi: 10.1007/s11060-014-1710-0. Epub 2015 Jan 8.

  PMID: 25567352 BACKGROUND

• Nghiemphu PL, Vitte J, Dombi E, Nguyen T, Wagle N, Ishiyama A, Sepahdari AR, Cachia D, Widemann BC, Brackmann DE, Doherty JK, Kalamarides M, Giovannini M. Imaging as an early biomarker to predict sensitivity to everolimus for progressive NF2-related vestibular schwannoma. J Neurooncol. 2024 Apr;167(2):339-348. doi: 10.1007/s11060-024-04596-4. Epub 2024 Feb 19.

  PMID: 38372904 DERIVED

MeSH Terms

Conditions

Neurofibromatosis 2; Neuroma, Acoustic

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nervous System Neoplasms; Neoplasms by Site; Peripheral Nervous System Neoplasms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Marco Giovannini, MD, PhD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2011
• First Posted: April 29, 2011
• Study Start: July 1, 2015
• Primary Completion: February 6, 2024
• Study Completion: February 6, 2024
• Last Updated: February 13, 2024

Record last verified: 2024-02

Locations

US (1)