GliomaPhase 2NCT00782626
Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas
A Phase 2 study testing everolimus in people with Glioma and Low-grade Glioma, run by Dana-Farber Cancer Institute at 10 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Glioma, Low-grade Glioma, Astrocytoma
- What is being tested?
- everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 10 sitesUnited States
- Study dates
- Jun 2009to Aug 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
John Hopkins Medical Center
Baltimore, Maryland, 21231
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
The Children's Hospital
Denver, Colorado, 80045
University of Florida College of Medicine
Gainesville, Florida, 32610
New York University
New York, New York, 10016
Memorial Sloan-Kettering Cancer Institute
New York, New York, 10174
Phoenix Children's Hospital Center for Cancer and Blood Disorders
Phoenix, Arizona, 85016
Doernbecher Children's Hospital Oregon Health & Science University
Portland, Oregon, 97239
Seattle Cancer Care Alliance
Seattle, Washington, 98109
About this study
Official title: A Phase II Study of Everolimus (RAD001) for Children With Chemotherapy and/or Radiation-Refractory Progressive or Recurrent Low-Grade Gliomas
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.
Read the detailed description
OBJECTIVES:
Primary
- To determine the response of children with chemotherapy-refractory or progressive low-grade gliomas to everolimus. Secondary
- To evaluate pharmacogenetic polymorphisms of cytochrome P450 3A4 \& 3A5 alleles and P-glycoprotein/MDR for their influence on the metabolism of everolimus in this patient population.
- To evaluate the role of Apolipoprotein E genotypes as predictors for development of hyperlipidemia during therapy with everolimus.
- To assess preliminary correlations of response with changes in pharmacodynamic parameters including p70s6 kinase activity in peripheral blood mononuclear cells.
- To describe the toxicity of everolimus when administered to this patient population.
- To characterize the pharmacokinetic profile of everolimus when administered to this patient population.
STATISTICAL DESIGN:
This study used a one-stage design to evaluate response to everolimus. If at least 3 responders are observed in 20 evaluable patients, then everolimus will be considered promising. If the true response rate is 5% (null hypothesis), the chance of concluding the treatment is active is 0.08 (Type I error). If the true response rate is 25% (alternative hypothesis), the chance of concluding the treatment is active is 0.91 (power).
- Conditions
- Glioma, Low-grade Glioma, Astrocytoma
- Being tested
- everolimus
- Keywords
- RAD001
- Medical subject headings
- Glioma, Astrocytoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
everolimusDrug
Also called RAD001
| Study group | Role | What they receive |
|---|---|---|
| everolimus | Experimental | Patients rcvd oral everolimus 5.0 mg/m2/day for a 28-day treatment course up to a total of 12 courses (48 weeks) if a patient had stable disease except if toxicity was unacceptable. Two dose reductions were permitted (3.0 5.0 mg/m2/day and 2.0 mg/m2/day). Receives: Drug: everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response
Overall response is classified as complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) on therapy.Description: Overall response is classified as complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) on therapy. Response for target lesions (up to5) is based on 3 dimensions with an elliptical model volume used: 0.5L*W*T; (L) tumor extent in plane perpendicular to the selected plane; (W) longest measurement of the tumor width; (T) transverse measurement perpendicular to the width. CR is disappearance all target and non-target lesions and no new lesions. PR is >/= 65% decrease in sum of the products (referent baseline). PD 40% or more increase in any target lesion (referent smallest product observed on therapy). SD is none of the above. PR and SD classification as long as absent new lesions and unequivocal progression for non-target lesions else PD.
Measured: Disease evaluations (MRI brain, including volumetric analysis) occurred at baseline, at the end of course 1, every 3 courses during treatment up to 12 courses and at early treatment discontinuation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2008 (estimated)
- Study startJun 2009
- Primary completionAug 2012
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GliomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis, The Pediatric Oncology Experimental Therapeutics Investigators' Consortium
- Responsible party
- Principal investigator, Karen D. Wright MD, Dana-Farber Cancer Institute
- Investigators
- Karen Wright, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00782626
- Sponsor's protocol ID
- 09-001
- Status last verified
- Jul 2018
- First submitted
- 29 Oct 2008
- Last updated
- 15 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Everolimus (RAD001) for Children With Chemotherapy and/or Radiation-Refractory Progressive or Recurrent Low-Grade Gliomas
- ClinicalTrials.gov ID
- NCT00782626
- Acronym / sponsor ID
- 09-001
- Conditions
- Glioma, Low-grade Glioma, Astrocytoma
- Keywords
- RAD001
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Novartis, The Pediatric Oncology Experimental Therapeutics Investigators' Consortium
- Study start
- Jun 2009
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 31 Oct 2008 (estimated)
- Results
- Posted 2 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
Primary
- To determine the response of children with chemotherapy-refractory or progressive low-grade gliomas to everolimus. Secondary
- To evaluate pharmacogenetic polymorphisms of cytochrome P450 3A4 \& 3A5 alleles and P-glycoprotein/MDR for their influence on the metabolism of everolimus in this patient population.
- To evaluate the role of Apolipoprotein E genotypes as predictors for development of hyperlipidemia during therapy with everolimus.
- To assess preliminary correlations of response with changes in pharmacodynamic parameters including p70s6 kinase activity in peripheral blood mononuclear cells.
- To describe the toxicity of everolimus when administered to this patient population.
- To characterize the pharmacokinetic profile of everolimus when administered to this patient population.
STATISTICAL DESIGN:
This study used a one-stage design to evaluate response to everolimus. If at least 3 responders are observed in 20 evaluable patients, then everolimus will be considered promising. If the true response rate is 5% (null hypothesis), the chance of concluding the treatment is active is 0.08 (Type I error). If the true response rate is 25% (alternative hypothesis), the chance of concluding the treatment is active is 0.91 (power).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| everolimus | Experimental | Drug: everolimusPatients rcvd oral everolimus 5.0 mg/m2/day for a 28-day treatment course up to a total of 12 courses (48 weeks) if a patient had stable disease except if toxicity was unacceptable. Two dose reductions were permitted (3.0 5.0 mg/m2/day and 2.0 mg/m2/day). |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| everolimusAlso: RAD001 | Drug | everolimus |
Primary outcome
Overall Response
Time frame: Disease evaluations (MRI brain, including volumetric analysis) occurred at baseline, at the end of course 1, every 3 courses during treatment up to 12 courses and at early treatment discontinuation.
Overall response is classified as complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) on therapy.Description: Overall response is classified as complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) on therapy. Response for target lesions (up to5) is based on 3 dimensions with an elliptical model volume used: 0.5L*W*T; (L) tumor extent in plane perpendicular to the selected plane; (W) longest measurement of the tumor width; (T) transverse measurement perpendicular to the width. CR is disappearance all target and non-target lesions and no new lesions. PR is >/= 65% decrease in sum of the products (referent baseline). PD 40% or more increase in any target lesion (referent smallest product observed on therapy). SD is none of the above. PR and SD classification as long as absent new lesions and unequivocal progression for non-target lesions else PD.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen Wright, MD principal investigator
Dana-Farber Cancer Institute
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing everolimus in people with Glioma and Low-grade Glioma, run by Dana-Farber Cancer Institute at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response (time frame: Disease evaluations (MRI brain, including volumetric analysis) occurred at baseline, at the end of course 1, every 3 courses during treatment up to 12 courses and at early treatment discontinuation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Aug 2018.