Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex

NCT00411619 | Completed Phase 1 Results DMC

• 1 other identifier: CCHMC IRB# 06-07-50
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the safety and potential side effects of everolimus (an experimental drug) on a person with Tuberous Sclerosis Complex who also has been diagnosed with a brain tumor (astrocytoma) The hypothesis is that the drug will cause the tumor size to decrease, and may have beneficial activity separate from effects on tumors in patients.

Conditions

Tuberous Sclerosis; Subependymal Giant Cell Astrocytoma

Keywords

Tuberous Sclerosis Complex (TSC); Subendymal Giant Cell Astrocytomas (SEGA'S); Mammalian Target of Rapamycin (mTOR); Everolimus (RAD001); Tuberous Sclerosis with Subependymal Giant Cell Astrocytomas

Outcome Measures

Primary Outcomes (1)

• Number With Observed Adverse Side Effects

  During the entire study

Secondary Outcomes (1)

• Overall Reduction in SEGA Tumor Volume.

  During the entire study

Study Arms (1)

Everolimus

EXPERIMENTAL

As this was a non-randomized, open-label, single arm study, all patients in the study received treatment with everolilmus

Drug: Everolimus

Interventions

Everolimus DRUG

Initial everolimus dosage will be 3 mg/m2/d taken daily or every other day, with titration to achieve a trough serum level of 5-15 ng/ml. Patients unable to tolerate levels in this range will have doses held or reduced 25% to achieve trough serum levels of 5-10 ng/ml. If trough serum level of 5-15 ng/ml is not achieved at a dosage of 3 mg/m2/d, then dosage escalation by 25% will be undertaken as tolerated. Everolimus will be similarly adjusted during the extension phase. If a subject misses more than 10 consecutive everolimus doses, additional days of everolimus treatment will be added so total duration of treatment is 6 months. If this occurs, dates of subsequent study events will be adjusted according to number of missed doses. This process will also be followed in the extension phase.

Also known as: RAD001

Everolimus

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age three years and older
• If female and of child bearing potential, documentation of negative pregnancy test prior to enrollment. In the extension phase, all females of child bearing potential will be required to take monthly home pregnancy tests and record results on a provided diary card.
• Clinically definite diagnosis of tuberous sclerosis (modified Gomez criteria or positive genetic test)
• Presence of giant cell astrocytoma as defined by imaging characteristics and serial increase in size of lesion on 2 or more MRI scans
• Adequate renal function (creatinine \< 1.5 mg/dl)

You may not qualify if:

• Serious intercurrent medical illness or other uncontrolled medical disease which could compromise participation in the study
• Significant hematologic or hepatic abnormality
• Continuous requirement for supplemental oxygen
• Intercurrent infection at initiation of everolimus
• Embolization of angiomyolipoma within one month; any other recent surgery within 2 months of initiation of everolimus
• Pregnant or lactating women
• Use of an investigational drug within the last 30 days
• Must be adequately recovered from the acute toxicities of any prior therapy
• Clinical evidence of impending herniation or focal neurologic deficit related to the subject's astrocytoma
• Unwilling or unable to use highly effective contraception

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Novartis: collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (6)

• Peters JM, Prohl A, Kapur K, Nath A, Scherrer B, Clancy S, Prabhu SP, Sahin M, Franz DN, Warfield SK, Krueger DA. Longitudinal Effects of Everolimus on White Matter Diffusion in Tuberous Sclerosis Complex. Pediatr Neurol. 2019 Jan;90:24-30. doi: 10.1016/j.pediatrneurol.2018.10.005. Epub 2018 Oct 18.

  PMID: 30424962 DERIVED

• Sparagana S, Franz DN, Krueger DA, Bissler JJ, Berkowitz N, Burock K, Kingswood JC. Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex. PLoS One. 2017 Oct 12;12(10):e0186235. doi: 10.1371/journal.pone.0186235. eCollection 2017.

  PMID: 29023494 DERIVED

• Franz DN, Agricola K, Mays M, Tudor C, Care MM, Holland-Bouley K, Berkowitz N, Miao S, Peyrard S, Krueger DA. Everolimus for subependymal giant cell astrocytoma: 5-year final analysis. Ann Neurol. 2015 Dec;78(6):929-38. doi: 10.1002/ana.24523. Epub 2015 Nov 9.

  PMID: 26381530 DERIVED

• Krueger DA, Care MM, Agricola K, Tudor C, Mays M, Franz DN. Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma. Neurology. 2013 Feb 5;80(6):574-80. doi: 10.1212/WNL.0b013e3182815428. Epub 2013 Jan 16.

  PMID: 23325902 DERIVED

• Tillema JM, Leach JL, Krueger DA, Franz DN. Everolimus alters white matter diffusion in tuberous sclerosis complex. Neurology. 2012 Feb 21;78(8):526-31. doi: 10.1212/WNL.0b013e318247ca8d. Epub 2012 Jan 18.

  PMID: 22262746 DERIVED

• Krueger DA, Care MM, Holland K, Agricola K, Tudor C, Mangeshkar P, Wilson KA, Byars A, Sahmoud T, Franz DN. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010 Nov 4;363(19):1801-11. doi: 10.1056/NEJMoa1001671.

  PMID: 21047224 DERIVED

MeSH Terms

Conditions

Tuberous Sclerosis; Astrocytoma; Hereditary Sensory and Autonomic Neuropathies

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. David Franz
• Organization: Cincinnati Children's Hospital Medical Center

david.franz@cchmc.org

513-636-4222

Study Officials

• David N Franz, M.D.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2006
• First Posted: December 14, 2006
• Study Start: January 1, 2007
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: October 20, 2014
• Results First Posted: October 20, 2014

Record last verified: 2014-10

Locations

US (1)