Everolimus (RAD001) for Children With Chemotherapy-Refractory Progressive or Recurrent Low-Grade Gliomas

NCT00782626 | Completed Phase 2 Results DMC

• 1 other identifier: 09-001
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Glioma; Low-grade Glioma; Astrocytoma

Keywords

RAD001

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Study Arms (1)

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).

Drug: everolimus

Interventions

everolimus DRUG

Also known as: RAD001

everolimus

Eligibility Criteria

• Age: 3 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Novartis: collaborator
• Pediatric Oncology Experimental Therapeutics Investigators' Consortium: collaborator

Study Sites (10)

Phoenix Children's Hospital Center for Cancer and Blood Disorders

Phoenix, Arizona, 85016, United States

Location

The Children's Hospital

Denver, Colorado, 80045, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

John Hopkins Medical Center

Baltimore, Maryland, 21231, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

New York University

New York, New York, 10016, United States

Location

Memorial Sloan-Kettering Cancer Institute

New York, New York, 10174, United States

Location

Doernbecher Children's Hospital Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Glioma; Astrocytoma

Interventions

Everolimus

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Mark Kieran
• Organization: Dana-Farber Cancer Institute

mark_kieran@dfci.harvard.edu

(617) 632-4907

Study Officials

• Karen Wright, MD

  Dana-Farber Cancer Institute

  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: Principal Investigator

Study Record Dates

• First Submitted: October 29, 2008
• First Posted: October 31, 2008
• Study Start: June 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: August 15, 2018
• Results First Posted: February 2, 2016

Record last verified: 2018-07

Locations

US (10)