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Trial record 5 of 84 for:    "Anaplastic ependymoma"

Everolimus for Children With Recurrent or Progressive Ependymoma

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ClinicalTrials.gov Identifier: NCT02155920
Recruitment Status : Recruiting
First Posted : June 4, 2014
Last Update Posted : May 3, 2018
Sponsor:
Information provided by (Responsible Party):
Daniel Bowers, University of Texas Southwestern Medical Center

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.

Condition or disease Intervention/treatment Phase
Recurrent Childhood Ependymoma Drug: Everolimus Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Everolimus (RAD001, Afinitor®) for Children With Recurrent or Progressive Ependymoma
Study Start Date : February 2015
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: Everolimus
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
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.
Other Name: RAD001, AFINITOR




Primary Outcome Measures :
  1. Objective Response Rate (Complete Response Rate and Partial Response Rate) following treatment with everolimus for children with recurrent or progressive ependymomas. [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Duration of response following treatment with everolimus for children with recurrent or progressive ependymomas. [ Time Frame: 2 years ]
  2. Progression free survival (PRS) following treatment with everolimus for children with recurrent or progressive ependymomas. [ Time Frame: 2 years ]
  3. Event free survival (EFS) following treatment with everolimus for children with recurrent or progressive ependymomas. [ Time Frame: 2 years ]
  4. Number of Participants with Adverse Events as a Measure of Safety and Tolerability. [ Time Frame: 2 years ]
  5. Correlation of tumor Objective Response Rate to established immunohistochemical biomarkers of mTOR pathway activation, including pS6, p4EBP1, pPRAS40, pp70S6K and PTEN. [ Time Frame: 2 years ]


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Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Tumor tissue must be available (from either time of initial diagnosis or relapse) and submitted for central pathology review and correlative biological studies.
  3. Performance status: Lansky ≥ 50% for patients ≤ 10 years of age or Karnofsky ≥ 50% for patients > 10 years of age.
  4. Adequate bone marrow, liver and renal function.
  5. 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.
  6. 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.
  7. 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.

Exclusion Criteria:

  1. Prior treatment with Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus).
  2. 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.
  3. Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus.
  4. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02155920


Locations
United States, California
Lucile Packard Children's Hospital Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Sonia Partap, MD    650-723-6841    spartap@stanford.edu   
United States, New York
New York University Stephen D. Hassenfeld Children's Center for Cancer & Blood Disorders Recruiting
New York, New York, United States, 10016
Contact: Matthias A Karajannis, MD    212-263-9959    Matthias.Karajannis@nyumc.org   
Contact: Melissa T Rosenhan, MPH    212-263-9931    Melissa.Rosenhan@nyumc.org   
United States, Texas
UT Southwestern Medical Center / Children's Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Daniel C Bowers, MD    214-456-6139    Daniel.Bowers@utsouthwestern.edu   
Contact: Natasha Anderson    214-456-6439    Natasha.Anderson@childrens.com   
Principal Investigator: Daniel C Bowers, MD         
Sub-Investigator: Laura J Klesse, MD, PhD         
Baylor College of Medicine / Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Jack M Su, MD    832-822-4306    jmsu@txch.org   
Contact: Murali M Chintagumpala, MD    832-825-1502    mxchinta@txch.org   
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Investigators
Principal Investigator: Daniel C Bowers, MD UT Southwestern Medical Center at Dallas, Dallas, TX

Responsible Party: Daniel Bowers, Professor of Pediatrics, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT02155920     History of Changes
Other Study ID Numbers: CRAD001CUS224T
First Posted: June 4, 2014    Key Record Dates
Last Update Posted: May 3, 2018
Last Verified: April 2018

Keywords provided by Daniel Bowers, University of Texas Southwestern Medical Center:
Ependymoma
Anaplastic Ependymoma

Additional relevant MeSH terms:
Ependymoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents