Everolimus for Children With NF1 Chemotherapy-Refractory Radiographic Progressive Low Grade Gliomas

NCT01158651 | Completed Phase 2 Results DMC

• 2 other identifiers: DOD W81XWH-05-1-0615UAB
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 12

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 in children with Neurofibromatosis type 1 (NF1). Additionally, the safety of RAD001 will be studied. The study drug, RAD001, is a drug that may act directly on tumor cells by preventing tumor cell growth and development. RAD001 has been studied in participants with various types of cancer as a single agent (a drug that is used alone to treat the cancer) or in combination with a number of well known anticancer therapies. Information from these research studies suggests that RAD001 may help to shrink or slow the growth of low-grade gliomas. In this research study, the investigators are looking to see the response of RAD001 in children with low-grade gliomas and NF1 that have either not responded to treatment or have come back after treatment. We are also looking for the highest dose of RAD001 that can be given safely in this patient population.

Conditions

Glioma

Keywords

NF1; low-grade glioma; progressive; children; NF Type 1 - low grade glioma - not responded to treatments

Outcome Measures

Primary Outcomes (1)

• RAD001 Response Rate Based on 2D MRI Change From Baseline

  Outcome is 2D MRI target tumor volume compared to baseline volume. Success criteria is volume less than 80% of baseline.

  Approximately 48 weeks

Secondary Outcomes (1)

• Common Terminology Criteria for Adverse Events (CTCAE) Events

  approximately 48 weeks

Study Arms (1)

RAD001 (Everolimus) Active Therapy

EXPERIMENTAL

If you take part in this research study, you will be given a participant diary for each treatment course to help you keep track of when you take your RAD001. You will be required to bring the completed diary at each scheduled visit. A treatment "course" lasts 4 weeks and there will not be any breaks between courses. You may stay on study for a total of 12 courses (48 weeks). You will take the study medication (tablets) by mouth, once a day during each course for as long as you are participating in this study. You will also be required to take an antibiotic during treatment to prevent infection.

Drug: RAD001 (Everolimus)

Interventions

RAD001 (Everolimus) DRUG

If you take part in this research study, you will be given a participant diary for each treatment course to help you keep track of when you take your RAD001. You will be required to bring the completed diary at each scheduled visit. A treatment "course" lasts 4 weeks and there will not be any breaks between courses. You may stay on study for a total of 12 courses (48 weeks). You will take the study medication (tablets) by mouth, once a day during each course for as long as you are participating in this study. You will also be required to take an antibiotic during treatment to prevent infection.

Also known as: RAD001, Everolimus

RAD001 (Everolimus) Active Therapy

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis: All patients must have a radiographically progressive low-grade glioma and at least two of the following diagnostic criteria for NF1, and/or a pathogenic NF1 gene mutation demonstrated in peripheral blood-derived DNA:
• Six or more café-au-lait spots (greater than or equal to 0.5 cm in prepubertal subjects or greater than or equal to 1.5 cm in postpubertal subjects)
• Freckling in the axilla and/or inguinal region
• Plexiform neurofibroma
• Two or more Lisch nodules
• A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)
• A first-degree relative with NF1
• An optic pathway glioma
• Disease Status: All patients must have radiographically progressive low-grade glioma (including NF1 related visual pathway gliomas) after failure of a carboplatin-containing regimen. Patients with recurrent/progressive disease do not require a biopsy to confirm the diagnosis.
• Evaluable or Measurable Disease: Patients must have at least one evaluable or measurable site of disease according to criteria described in Section 9. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation.
• Age: Patients must be greater than 1 years and less than or equal to 21 years of age at the time of study entry.
• Performance Level: Karnofsky 50% for patients greater than 10 years of age and Lansky 50% for patients 10 years of age (Appendix I). Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy
• Patients must have failed or not been able to tolerate a carboplatin-based regimen.
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy or radiotherapy prior to entering this study.

You may not qualify if:

• Chronic treatment with systemic steroids or another immunosuppressive agent. Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary.
• Evidence of an active lesion including: plexiform neurofibroma, malignant peripheral nerve sheath tumor, or other cancer requiring concurrent treatment with chemotherapy or radiation therapy. Patients not requiring treatment for these lesions are eligible for this protocol.
• Patients who:
• have had a major surgery or significant traumatic injury within 2 weeks of start of study drug;
• have not recovered from the side effects of any major surgery (defined as requiring general anesthesia but excluding a procedure for insertion of central venous access), or
• may require major surgery during the course of the study.
• Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
• Patients with an active, bleeding diathesis or on oral anti-vitamin K medication (except low dose coumarin).
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
• symptomatic congestive heart failure of New York heart Association Class III or IV.
• unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
• severely impaired lung function.
• uncontrolled diabetes as defined by fasting serum glucose greater than 1.5x ULN.
• active (acute or chronic) or uncontrolled severe infections.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Boston Children's Hospital: collaborator
• Children's Hospital of Philadelphia: collaborator
• Children's National Research Institute: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator
• National Cancer Institute (NCI): collaborator
• University of Chicago: collaborator
• University of Utah: collaborator
• Washington University School of Medicine: collaborator
• Ann & Robert H Lurie Children's Hospital of Chicago: collaborator
• NYU Langone Health: collaborator
• Children's Hospital Los Angeles: collaborator

Study Sites (12)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Lurie Hospital

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

National Cancer Institute

Bethesda, Maryland, 20892, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19096, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Glioma

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: Karen Cole-Plourde
• Organization: UAB

kplourde@uab.edu

205-934-5140

Study Officials

• Bruce R. Korf, MD, PhD

  The University of Alabama at Birmingham

  STUDY CHAIR

• Mark Kieran, MD

  Boston Children's Hospital

  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: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 2, 2010
• First Posted: July 8, 2010
• Study Start: July 10, 2010
• Primary Completion: September 4, 2014
• Study Completion: October 26, 2017
• Last Updated: February 5, 2020
• Results First Posted: February 5, 2020

Record last verified: 2020-01

Locations

US (12)