Clinical Trial: Everolimus for Children With Recurrent or Progressive Ependymoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase II Study of Everolimus (RAD001, Afinitor®) for Children With Recurrent or Progressive Ependymoma

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.

Detailed Summary:

Ependymoma is the third most common central nervous system neoplasm in children, accounting for approximately 10% of childhood brain tumors. Although the prognosis for children with newly-diagnosed completely resected ependymomas is often good, children with incompletely resected tumors often suffer repeated episodes of tumor progression and die as a result of their tumor. The prognosis for children with recurrent or progressive ependymomas is especially dismal and the majority of children with recurrent or progressive ependymomas will eventually succumb to their tumor within 8.7 to 24 months. At the time of tumor recurrence, therapeutic options are limited. A recent report by Merchant and co-workers described several long-term survivors after tumor recurrence when treated with a second course of radiation therapy.

Unfortunately, although chemotherapy occasionally demonstrates anti-tumor activity against recurrent ependymoma, but responses are rarely durable.12 Indeed, a recent review by Bouffet and co-workers concluded that the frequency of durable responses of recurrent ependymomas to chemotherapy was disappointing and encouraged a re-evaluation of the current chemotherapeutic approach to intracranial ependymoma and that studies are needed to identify new biological targets to inform future clinical trials.

Everolimus is a novel derivative of rapamycin. It has been in clinical development since 1996 as an immunosuppressant in solid organ transplantation. Everolimus is approved in Europe and other global markets (trade name: Certican®) for cardiac and renal transplantation, and in the United States (trade name: Zortress®) for the prevention of organ rejection of kidney transplantation. Everolimus was developed in oncology as Afinitor® and was approved for advanced renal cell carcinoma (RCC) in 2009. In 2010
Sponsor: University of Texas Southwestern Medical Center

Current Primary Outcome: 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 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Duration of response following treatment with everolimus for children with recurrent or progressive ependymomas. [ Time Frame: 2 years ]
  • Progression free survival (PRS) following treatment with everolimus for children with recurrent or progressive ependymomas. [ Time Frame: 2 years ]
  • Event free survival (EFS) following treatment with everolimus for children with recurrent or progressive ependymomas. [ Time Frame: 2 years ]
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability. [ Time Frame: 2 years ]
  • 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 ]


Original Secondary Outcome: Same as current

Information By: University of Texas Southwestern Medical Center

Dates:
Date Received: May 29, 2014
Date Started: February 2015
Date Completion: December 2019
Last Updated: December 2, 2016
Last Verified: December 2016