PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01734512 |
Recruitment Status
:
Recruiting
First Posted
: November 27, 2012
Last Update Posted
: April 13, 2018
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Pediatric Recurrent Progressive Low-grade Gliomas Pediatric Progressive Low-grade Gliomas | Drug: Everolimus | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 65 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children |
Study Start Date : | November 2012 |
Estimated Primary Completion Date : | November 2019 |
Estimated Study Completion Date : | November 2022 |
Arm | Intervention/treatment |
---|---|
Experimental: Everolimus
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 BSA (body surface area) 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
Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
|
- Evaluation of efficacy by Progression Free Survival associated with everolimus therapy [ Time Frame: up to 6 months ]Determined by 6-month progression free survival. Response will 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.
- Estimation of Objective Response - Progression Free Survival [ Time Frame: Up to 6 weeks ]Estimate Progression Free Survival distribution along with objective response rates associated with everolimus treatment.
- Exploration of Associations with pS6 Positivity and Outcome [ Time Frame: Up to 6 months ]Explore associations between pS6 positivity and outcome as measured by the 6-month disease stabilization rates and Progression Free Survival.
- Estimation of Objective Response - Overall Survival [ Time Frame: Up to 6 weeks ]Estimate Overall Survival distributions along with objective response rates associated with everolimus treatment.
- Tissue Collection [ Time Frame: Up to 8 Years ]Collect tissue from ALL enrolled patients and prospectively analyze key molecular features including activation of the PI3K, mTOR and MAPK pathways, aberrations in PTEN, IDH1, and IDH2, and activating mutations in BRAF (KIAA1549-BRAF fusion and BRAFV600E missense BRAF mutation).
- Quantitative measures of cerebral blood [ Time Frame: Up to 6 weeks ]Explore MR quantitative measures of relative cerebral blood volume, permeability and apparent diffusion coefficient within the region of hyper-intensity on T2-weighted images as markers of disease response and/or progression in comparison to institutional evaluation of disease response and/or progression and quantitative measures of tumor response as determined by central review (based upon both area and volumetric measures.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 3 Years to 21 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
--Patients must have radiographic progressive or recurrent confirmed WHO grade I or II astrocytomas, that was confirmed histologically at initial diagnosis. 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, 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.
- Life expectancy of greater than 8 weeks.
- Patients must be able to swallow pills.
- Patient must have a Karnofsky (if ≥ 16 years of age) or Lansky Performance score (if ≤ 16 years of age) of ≥50 by the time of registration.
- Patients must have adequate bone marrow function (ANC ≥ 1,000/mm3, platelet count of ≥ 100,000/mm3, and hemoglobin ≥ 9 gm/dL) before starting therapy. Eligibility level for hemoglobin may be reached by transfusion.
- INR ≤1.5. (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks at time of randomization).
- Patients must have adequate liver function (SGPT/ALT ≤ 2.5 times ULN and bilirubin ≤ 1.5 times ULN) before starting therapy.
- Patients must have adequate renal function (serum creatinine ≤ 1.5 times institutional ULN for age or GFR ≥ 70 ml/min/1.73 m2) before starting therapy.
- Patients must have cholesterol level <350 mg/dL and triglycerides < 400 mg/dL before starting therapy. In case one or both of these are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication and documentation of cholesterol < 350mg/dL and triglycerides < 400mg/dl before start of therapy.
- Patients must have normal pulmonary function testing for age based on pulse oximetry.
- The effects of everolimus on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because everolimus are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
- Female patients of child bearing potential must not be breastfeeding or pregnant as evidenced by a negative pregnancy test.
Exclusion Criteria:
- 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, 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.
- Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01734512
Contact: Sabine Mueller, MD | 415-476-3831 | sabine.mueller@ucsf.edu | |
Contact: PNOC Regulatory | 415-502-1600 | PNOC_Regulatory@ucsf.edu |
United States, California | |
Children's Hospital Los Angeles | Recruiting |
Los Angeles, California, United States, 90027 | |
Contact: Ghirish Dhall, MD 323-361-8147 GDhall@chla.usc.edu | |
Contact: Ashley Margol, MD amargol@chla.usc.edu | |
Principal Investigator: Ghirish Dhall, MD | |
Sub-Investigator: Ashley Margol, MD | |
University of California, Los Angeles | Recruiting |
Los Angeles, California, United States, 90027 | |
Contact: Tom B Davidson, MD 310-825-6708 tdavidson@mednet.ucla.edu | |
Contact: Anthony Wang acwang@mednet.ucla.edu | |
Principal Investigator: Tom B Davidson, MD | |
Sub-Investigator: Anthony Wang, MD | |
Children's Hospital Oakland | Recruiting |
Oakland, California, United States, 94609 | |
Contact: Joseph Torkildson, MD 510-428-3272 jtorkildson@mail.cho.org | |
Contact: Caroline Hastings, MD (510) 428-3272 chastings@mail.cho.org | |
Principal Investigator: Joseph Torkildson, MD | |
Sub-Investigator: Caroline Hastings, MD | |
University of California, San Diego Rady Children's Hospital | Recruiting |
San Diego, California, United States, 92123 | |
Contact: John Crawford, MD 858-966-4930 jrcrawford@rchsd.org | |
Contact: Janet Yoon, MD jyoon@rchsd.org | |
Principal Investigator: John Crawford, MD | |
Sub-Investigator: Janet Yoon, MD | |
University of California, San Francisco | Recruiting |
San Francisco, California, United States, 94158 | |
Contact: Sabine Mueller, MD 415-476-3831 sabine.mueller@ucsf.edu | |
Contact: Anu Banerjee, MD anu.banerjee@ucsf.edu | |
Principal Investigator: Sabine Mueller, MD | |
Sub-Investigator: Anu Banerjee, MD | |
United States, District of Columbia | |
Children's National Medical Center | Not yet recruiting |
Washington, District of Columbia, United States, 20010 | |
Contact: Lindsay Kilburn, MD 202-476-3854 lkilburn@cnmc.org | |
Contact: Roger Packard, MD rpackard@nmc.org | |
Principal Investigator: Lindsay Kilburn, MD | |
Sub-Investigator: Roger Packard, MD | |
United States, Illinois | |
Ann & Robert H. Lurie Children's Hospital of Chicago | Recruiting |
Chicago, Illinois, United States, 60611 | |
Contact: Stewart Goldman, MD 312-227-4873 sgoldman@luriechildrens.org | |
Contact: Jason Fangusaro, MD jfangusaro@luriechildrens.org | |
Principal Investigator: Stewart Goldman, MD | |
Sub-Investigator: Jason Fangusaro, MD | |
United States, Massachusetts | |
Dana-Farber Cancer Institute | Recruiting |
Boston, Massachusetts, United States, 02215 | |
Contact: Susan Chi, MD 617-632-2291 susan_chi@dfci.harvard.edu | |
Contact: Daphne Haas-Kogan, MD dhaas-kogan@lroc.harvard.edu | |
Principal Investigator: Susan Chi, MD | |
Sub-Investigator: Daphne Haas-Kogan, MD | |
United States, Minnesota | |
Children's Hospitals and Clinics of Minneapolis | Recruiting |
Minneapolis, Minnesota, United States, 55404 | |
Contact: Christopher Moertel, MD 612-626-2778 moert001@umn.edu | |
Contact: Anne Bendel, MD 612-813-5940 anne.bendel@childrensmn.org | |
United States, Missouri | |
St. Louis Children's Hospital, Washington University | Recruiting |
Saint Louis, Missouri, United States, 63130 | |
Contact: Karen Gauvain, MD 314-286-2790 gauvain_k@kids.wustl.edu | |
Contact: Josh Rubin, MD rubin_j@kids.wustl.edu | |
Principal Investigator: Karen Gauvain, MD | |
Sub-Investigator: Josh Rubin, MD | |
United States, Ohio | |
Nationwide Children's Hospital | Recruiting |
Columbus, Ohio, United States, 43205 | |
Contact: Jonathan Finlay, MD 614-722-4087 jonathan.finlay@nationwidechildrens.org | |
Contact: Mohamed AbdelBaki, MD mohamed.abdelbaki@NationwideChildrens.org | |
Principal Investigator: Jonathan Finlay, MD | |
Sub-Investigator: Mohamed AbdelBaki, MD | |
United States, Oregon | |
Oregon Health & Science University | Recruiting |
Portland, Oregon, United States, 97239 | |
Contact: Kellie Nazemi, MD 503-494-1543 nazemik@ohsu.edu | |
Principal Investigator: Kellie Nazemi, MD | |
United States, Pennsylvania | |
The Children's Hospital Of Philadelphia | Recruiting |
Philadelphia, Pennsylvania, United States, 19104 | |
Contact: Jane Minturn, MD, PhD 267-426-5026 MINTURN@email.chop.edu | |
Contact: Michael Fisher, MD FISHERM@email.chop.edu | |
Principal Investigator: Jane Minturn, MD, PhD | |
Sub-Investigator: Michael Fisher, MD | |
United States, Tennessee | |
St. Jude Children's Research Hospital | Recruiting |
Memphis, Tennessee, United States, 38105 | |
Contact: Amar Gajjar, MD 901-595-2615 Amar.Gajjar@STJUDE.ORG | |
Contact: Ibrahim Qaddoumi, MD 901-595-2365 ibrahim.qaddoumi@stjude.org | |
Principal Investigator: Amar Gajjar, MD | |
Sub-Investigator: Ibrahim Qaddoumi, MD | |
United States, Utah | |
University of Utah | Recruiting |
Salt Lake City, Utah, United States, 84112 | |
Contact: Richard Lemons, MD 801-662-4700 richard.lemons@intermountainmail.org | |
Contact: Carol Bruggers, MD 801-662-4700 carol.bruggers@imail.org | |
Principal Investigator: Richard Lemons, MD | |
Sub-Investigator: Carol Bruggers, MD | |
United States, Washington | |
University of Washington, Seattle | Recruiting |
Seattle, Washington, United States, 98195 | |
Contact: Sarah Leary, MD 206-667-7955 sarah.leary@seattlechildrens.org | |
Contact: Russ Geyer, MD 206-667-7955 russ.geyer@seattlechildrens.org | |
Principal Investigator: Sarah Leary, MD | |
Sub-Investigator: Russ Geyer, MD |
Study Chair: | Daphne Haas-Kogan, MD | Harvard University Dana-Farber Institute | |
Principal Investigator: | Sabine Mueller, MD | University of California, San Francisco |
Responsible Party: | University of California, San Francisco |
ClinicalTrials.gov Identifier: | NCT01734512 History of Changes |
Other Study ID Numbers: |
CC#120817 |
First Posted: | November 27, 2012 Key Record Dates |
Last Update Posted: | April 13, 2018 |
Last Verified: | April 2018 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes | |
Studies a U.S. FDA-regulated Device Product: | No | |
Product Manufactured in and Exported from the U.S.: | No |
Keywords provided by University of California, San Francisco:
pediatric recurrent progressive low-grade gliomas pediatric progressive low-grade gliomas everolimus mTOR inhibition |
Additional relevant MeSH terms:
Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Everolimus |
Sirolimus Antineoplastic Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Anti-Bacterial Agents Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents |