PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children

NCT01734512 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 120817NCI-2012-02774
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 18

Brief Summary

This is an open label study of everolimus in children with recurrent or progressive low-grade glioma.

Conditions

Pediatric Recurrent Progressive Low-grade Gliomas; Pediatric Progressive Low-grade Gliomas

Keywords

pediatric recurrent progressive low-grade gliomas; pediatric progressive low-grade gliomas; everolimus; mTOR inhibition

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Progression Free Survival at 6 Months

  Response was be determined by bi-dimensional diameters. RECIST criteria will be collected and used for secondary evaluation. Patients will have brain MRI scans with and without gadolinium performed prior to therapy, after every second course in the first year, after every third course in the second year, and at the End of Study visit (if not done within prior 3 months). Spine MRIs should be performed prior to therapy and at the same time points as standard brain MRIs if clinically indicated.

  Up to 6 months

Secondary Outcomes (4)

• Proportion of Participants With Objective Response

  Up to 6 months

• Median Progression Free Survival in Recurrent Pediatric Low-grade Glioma (LGGs)

  Up to 5 years

• Median Overall Survival From Time of Diagnosis

  Up to 5 years

• Median Overall Survival From Time of Enrollment

  Up to 5 years

Study Arms (1)

Everolimus

EXPERIMENTAL

Everolimus tablet will be taken daily by mouth with water. Twenty-eight days will constitute one course and subsequent courses will immediately follow with no break in the administration of the drug. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. Patients will also be provided with a drug diary for everolimus. The maximum time on study is 24-months, but if there is no disease progression or adverse events, the patient may speak with a doctor about continuing the treatment off-study.

Drug: Everolimus

Interventions

Everolimus DRUG

Everolimus tablet will be taken daily by mouth with water. All participants will be given a dose of 5 mg/m2/dose daily.

Also known as: Zortress, Afinitor

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 radiographic progressive or recurrent confirmed world health organization (WHO) grade I or II astrocytomas, that was confirmed histologically. Progressive or recurrent disease should be based on MRI according to the definition below.
• Eligible histologies:
• Pilocytic Astrocytoma - 90600112
• Astrocytoma, Low Grade (Fibrillary astrocytoma, WHO Grade 2) - 10065886
• Astrocytoma, Low Grade (Low-grade Astrocytoma, not otherwise specified (NOS), WHO Grade 2) - 10003571
• Tissue from the initial diagnosis or recurrence must be made available for correlative testing.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions on MRI.
• Patients may have had treatment (chemotherapy and/or radiotherapy) for any number of relapses prior to this recurrence.
• Patients must have received their last dose of myelosuppressive anticancer chemotherapy at least three (3) weeks prior to study registration or at least six (6)weeks of nitrosourea.
• Patients must have received their last dose of other investigational or biological agent \> 7 days prior to study entry.
• For agents that have known adverse events occurring beyond 7 days after administration, this period should be extended beyond the time during which adverse events are known to occur. This should be discussed with the study chair.
• If patients received prior monoclonal antibody treatment, at least three half-lives must be elapsed by the time of treatment initiation. These patients should also be discussed with the study chair.
• Patients must have received their last fraction of craniospinal or focal radiation to primary tumor or other sites \>12 weeks (3 months) prior to registration.
• Age ≥3 and ≤21 years.
• Because no dosing or adverse event data are currently available on the use of everolimus in patients \<3 years of age, these young children are excluded from this study.

You may not qualify if:

• Patients with primary spinal cord tumors
• Patients receiving concomitant medication that may interfere with study outcome. For example, patients cannot be on enzyme inducing anticonvulsants like phenytoin.
• Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, bacille Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
• Hepatitis B/C blood test must be done at screening for all patients. Patients who test positive for Hepatitis C antibodies and the Hepatitis B antigen are ineligible.
• A known history of HIV seropositivity. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with everolimus. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
• Patients may not have therapy for this recurrence (including radiation).
• Patients who do not have measurable disease on MRI.
• Patients who have been previously treated with an mTOR inhibitor.
• Patients with a known hypersensitivity to everolimus or other rapamycins (e.g. sirolimus, temsirolimus).
• Patients receiving any other concurrent anticancer or investigational therapy.
• Patients with any clinically significant unrelated systemic illness that would compromise the patient's ability to tolerate protocol therapy.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection.
• Patients with inability to return for follow-up visits to assess toxicity to therapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Novartis Pharmaceuticals: collaborator
• Pacific Pediatric Neuro-Oncology Consortium: collaborator
• The Pediatric Low Grade Astrocytoma (PLGA) Foundation: collaborator

Study Sites (18)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

University of California, Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Oakland

Oakland, California, 94609, United States

Location

University of California, San Diego Rady Children's Hospital

San Diego, California, 92123, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Children's National Medical Center

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

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21218, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Children's Hospitals and Clinics of Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

St. Louis Children's Hospital, Washington University

St Louis, Missouri, 63130, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

The Children's Hospital Of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Washington, Seattle

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Haas-Kogan DA, Aboian MS, Minturn JE, Leary SES, Abdelbaki MS, Goldman S, Elster JD, Kraya A, Lueder MR, Ramakrishnan D, von Reppert M, Liu KX, Rokita JL, Resnick AC, Solomon DA, Phillips JJ, Prados M, Molinaro AM, Waszak SM, Mueller S. Everolimus for Children With Recurrent or Progressive Low-Grade Glioma: Results From the Phase II PNOC001 Trial. J Clin Oncol. 2024 Feb 1;42(4):441-451. doi: 10.1200/JCO.23.01838. Epub 2023 Nov 17.

  PMID: 37978951 DERIVED

MeSH Terms

Interventions

Everolimus

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Dr. Sabine Mueller, MD, PhD
• Organization: University of California, San Francisco

sabine.mueller@ucsf.edu

(415) 502-7301

Study Officials

• Daphne Haas-Kogan, MD

  Dana-Farber Cancer Institute

  STUDY CHAIR

• Sabine Mueller, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2012
• First Posted: November 27, 2012
• Study Start: December 13, 2012
• Primary Completion: January 31, 2020
• Study Completion: July 31, 2024
• Last Updated: September 9, 2025
• Results First Posted: February 18, 2021

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)