Everolimus for Children With Recurrent or Progressive Ependymoma

NCT02155920 | Completed Phase 2 Results DMC

• 1 other identifier: STU 052014-038
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to evaluate the anti-tumor activity of Everolimus among children with recurrent or progressive ependymoma. Recurrent or progressive ependymoma is incurable and has very limited treatment options. The rationale for this study is based upon both pre-clinical and clinical considerations: Immunohistochemistry studies have demonstrated that 20 out of 23 (87%) pediatric ependymomas are immunoreactive for phosphorylated S6, a biomarker that often predicts response to mTOR pathway-targeted therapy. Furthermore, children with with multiply recurrent ependymomas have had objective and durable responses to the mTOR inhibitor, Sirolimus (Rapamune, Pfizer). As a result of this pre-clinical and clinical data, this study will further investigate the activity of an mTOR pathway inhibitor, Everolimus, against children with recurrent or progressive ependymomas. In this study, Everolimus will be administered at a dose and schedule that have previously been demonstrated as safe and effective in children. Children may take Everolimus for up to 2 years on this study, until tumor progression or unacceptable toxicity.

Conditions

Recurrent Childhood Ependymoma

Keywords

Ependymoma; Anaplastic Ependymoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (Complete Response Rate and Partial Response Rate) Following Treatment With Everolimus for Children With Recurrent or Progressive Ependymomas.

  Complete Response: Disappearance of all enhancing measurable and non-measurable disease Partial Response: ≥50% decrease in sum of products of perpendicular diameters of all measurable enhancing lesions compared with baseline

  2 years

Secondary Outcomes (5)

• Duration of Response

  2 years

• Progression Free Survival (PRS)

  2 years

• Event Free Survival (EFS)

  2 years

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability.

  2 years

• Number of Participants With Upregulated Biomarkers of mTOR Activation

  2 years

Study Arms (1)

Everolimus

EXPERIMENTAL

The recommended dose of Everolimus is 4.5 mg/m2/dose, once daily for up to 2 years, until disease progression or unacceptable toxicity occurs.

Drug: Everolimus

Interventions

Everolimus DRUG

The recommended dose of Everolimus is 4.5 mg/m2/dose, once daily for up to 2 years, until disease progression or unacceptable toxicity occurs.

Also known as: RAD001, AFINITOR

Everolimus

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis and Age: Ependymoma (WHO grade II) or Anaplastic Ependymoma (WHO grade III) that has relapsed or become refractory to standard therapy. Patients must have had histologic verification of their malignancy at original diagnosis or time of recurrence. Age must be ≥ 2 years and ≤ 21 years of age at study entry.
• Tumor tissue must be available (from either time of initial diagnosis or relapse) and submitted for central pathology review and correlative biological studies.
• Performance status: Lansky ≥ 50% for patients ≤ 10 years of age or Karnofsky ≥ 50% for patients \> 10 years of age.
• Adequate bone marrow, liver and renal function.
• Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x the upper limit of normal. 6. Patients must have measurable residual disease, defined as tumor that is measurable in two diameters on MRI. Diffuse leptomeningeal disease is not considered measurable.
• Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, and radiotherapy prior to participating in this trial. No prior myelosuppressive chemotherapy for 28 days prior to study enrollment. Must not have received craniospinal radiation therapy within 24 weeks prior to study entry and no involved field radiation therapy for 12 weeks prior to study enrollment. If patients received prior monoclonal antibody treatment, at least three half-lives must be elapsed by the time of treatment initiation. No investigational drugs for 4 weeks prior to study enrollment.
• MRI of the brain and the complete spine: All patients must have an MRI of the brain and spine that has measurable tumor (not only diffuse leptomeningeal tumor) within two weeks prior to study enrollment.

You may not qualify if:

• Prior treatment with Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus).
• Concommitant use of medications known to have inhibition or induction of CYP3A enzymes. Systemic corticosteroids (e.g., dexamethasone is a CYP3A inducer) are not allowed. Inhaled corticosteroids are allowed.
• Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus.
• Uncontrolled diabetes mellitus as defined by HbA1c \> 8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (4)

Lucile Packard Children's Hospital Stanford University

Stanford, California, 94305, United States

Location

New York University Stephen D. Hassenfeld Children's Center for Cancer & Blood Disorders

New York, New York, 10016, United States

Location

UT Southwestern Medical Center / Children's Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine / Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Bowers DC, Rajaram V, Karajannis MA, Gardner SL, Su JM, Baxter P, Partap S, Klesse LJ. Phase II study of everolimus for recurrent or progressive pediatric ependymoma. Neurooncol Adv. 2023 Feb 10;5(1):vdad011. doi: 10.1093/noajnl/vdad011. eCollection 2023 Jan-Dec.

  PMID: 36950217 DERIVED

MeSH Terms

Conditions

Familial ependymoma; Ependymoma

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

The study population largely consisted of PF-A tumors (which have a by far worse outcome with standard primary therapy) that has been heavily pretreated with multiple regimens of both chemotherapy and radiation therapy. The study is unable to comment upon whether mTOR pathway-targeted therapy has activity against PF-B ependymoma or newly diagnosed tumors. Finally, it is possible that a newer generation mTOR targeting agent may yet have activity against pediatric ependymoma.

Results Point of Contact

• Title: Daniel C. Bowers, MD
• Organization: University of Texas Southwestern Medical School

Daniel.Bowers@utsouthwestern.edu

214-648-3896

Study Officials

• Daniel C Bowers, MD

  UT Southwestern Medical Center at Dallas, Dallas, TX

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: May 29, 2014
• First Posted: June 4, 2014
• Study Start: February 1, 2015
• Primary Completion: July 14, 2023
• Study Completion: July 14, 2023
• Last Updated: May 8, 2024
• Results First Posted: May 8, 2024

Record last verified: 2024-04

Locations

US (4)