Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas
This study has been completed.
Pediatric Oncology Experimental Therapeutics Investigators' Consortium
Information provided by (Responsible Party):
Mark W. Kieran, MD, PhD, Dana-Farber Cancer Institute
First received: October 29, 2008
Last updated: December 4, 2012
Last verified: December 2012
The purpose of this research study is to learn if the study drug RAD001 can shrink or slow the growth of low-grade gliomas. Additionally, the safety of RAD001 will be studied. RAD001 is a drug that may act directly on tumor cells by inhibiting tumor cell growth and proliferation.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase II Study of Everolimus (RAD001) for Children With Chemotherapy and/or Radiation-Refractory Progressive or Recurrent Low-Grade Gliomas
Primary Outcome Measures:
- To determine the response of children with chemotherapy-refractory or progressive low-grade gliomas to RAD001. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- To describe the toxicity of RAD001 when administered to this patient population [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- To characterize the pharmacokinetic profile of RAD001 when administered to this patient population [ Time Frame: 3 years ] [ Designated as safety issue: No ]
| Study Start Date:
| Primary Completion Date:
||August 2012 (Final data collection date for primary outcome measure)
Taken orally oncea day. A treatment course will consist of 4 weeks of therapy and may be repeated up to 12 total courses (48 weeks).
Other Name: Everolimus
- Participants will be given a study medication-dosing calendar for each treatment course. Each treatment course lasts 4 weeks. Participants can remain on study for 12 courses (48 weeks). Participants will take RAD001 tablets orally once a day. If participants cannot swallow tablets, participants will be instructed on how to create a liquid preparation.
- During all treatment courses participants will have a physical exam. Each treatment course lasts 4 weeks. A medical history, urine test, blood tests, ECG and tumor imaging using MRI and MR Perfusion and Diffusion will also be performed. Blood sampling for RAD001 levels will be drawn weekly during the first course (4 weeks) of treatment and then drawn once during subsequent courses thereafter.
- Pharmacokinetic studies will be done to see how the body absorbs, distributes and excretes RAD001 by measuring the amount of the drug in the body at different time points after taking the medication. Blood will be drawn one time before the start of RAD001 therapy. Blood samples will also be drawn on Day 1 of cycle 2 at the following times: before the Day 1 dose (pre-dose), 2, and 5 hours after the Day 1 dose of RAD001.
|Ages Eligible for Study:
||3 Years to 21 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Patients must have histologic verification of one of the eligible diagnoses listed here: Astrocytoma variants; fibrillary, protoplasmic, mixed: Pilocytic astrocytoma; including pilomyxoid variants: Pleomorphic xanthoastrocytoma: infantile desmoplastic astrocytoma: ganglioglioma: oligodendroglial tumors: mixed glioma.
- Patients must have received at least one cancer-directed therapy and patients with allergies to carboplatin must have demonstrated progressive disease after cessation of therapy.
- Must have at least one measurable site of disease that has not been previously irradiated. If the patient has previous irradiation to the marker lesion(s), there must be evidence of progression since radiation treatment.
- Patients must be between 3 years of age and 21 years of age
- Karnofsky Performance Status of 50% or greater for patients less than 10 years of age or Lansky Score of 50% or greater for patients 10 and up.
- Participants must have recovered from the acute toxic effects of all prior chemotherapy or radiotherapy prior to entering the study. Refer to protocol for specific time restrictions with prior therapy completion.
- Adequate bone marrow function as defined in protocol
- Adequate renal function as defined in protocol
- Adequate liver function as defined in protocol
- Patients must have a fasting LDL cholesterol within the normal range per institutional guidelines
- Patients taking cholesterol lowering agent must be on a single medication and on a stable dose for at least 4 weeks
- Fasting serum cholesterol as outlined in protocol
- Patients must not be taking enzyme-inducing anticonvulsants
- Patients may not be currently receiving strong inhibitors of CYP3A4
- Presence of NF1 by clinical examination or by genetic testing
- Patients who have had a major surgery or significant traumatic injury within 2 weeks of start of study drug, patients who have not recovered from teh side effects of any major surgery, or patients that may require major surgery during the course of the study
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled are allowed
- Evidence of plexiform neurofibroma, malignant peripheral nerve sheath tumor, or other cancer requiring treatment with chemotherapy or radiation therapy
- Uncontrolled brain or leptomeningeal metastases from plexiform neurofibromas, malignant peripheral nerve sheath tumors, or other cancers (other than astrocytoma variants; fibrillary, protoplasmic, mixed: Pilocytic astrocytoma; including pilomyxoid variants: Pleomorphic xanthoastrocytoma: infantile desmoplastic astrocytoma: ganglioglioma: oligodendroglial tumors: mixed glioma), including patients who continue to require glucocorticoids for control of symptoms related to brain or leptomeningeal metastases.
- Other malignancies within the past three 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 or other conditions that could affect their participation in the study (see protocol for examples)
- Known history of HIV seropositivity
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
- Active, bleeding diathesis or oral anti-vitamin K medication (except low dose coumarin)
- Female patients who are pregnant or breast feeding
- Prior treatment with an mTOR inhibitor
- Known hypersensitivity to RAD001 or other rapamycins or to is excipients
- Dental braces or prosthesis that interferes with tumor imaging
- Patients with a positive history of Hepatitis B or Hepatitis C
- Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00782626
|Phoenix Children's Hospital Center for Cancer and Blood Disorders
|Phoenix, Arizona, United States, 85016 |
|The Children's Hospital
|Denver, Colorado, United States, 80045 |
|University of Florida College of Medicine
|Gainesville, Florida, United States, 32610 |
|Children's Healthcare of Atlanta
|Atlanta, Georgia, United States, 30322 |
|John Hopkins Medical Center
|Baltimore, Maryland, United States, 21231 |
|Dana-Farber Cancer Institute
|Boston, Massachusetts, United States, 02115 |
|Memorial Sloan-Kettering Cancer Institute
|New York, New York, United States, 10174 |
|New York University
|New York, New York, United States, 10016 |
|Doernbecher Children's Hospital Oregon Health & Science University
|Portland, Oregon, United States, 97239 |
|Seattle Cancer Care Alliance
|Seattle, Washington, United States, 98109 |
Dana-Farber Cancer Institute
Pediatric Oncology Experimental Therapeutics Investigators' Consortium
||Mark W. Kieran, MD, PhD
||Dana-Farber Cancer Institute
No publications provided
||Mark W. Kieran, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 29, 2008
||December 4, 2012
||United States: Food and Drug Administration
Keywords provided by Dana-Farber Cancer Institute:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 23, 2013
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Physiological Effects of Drugs