Trial Outcomes & Findings for PNOC 001: Phase II Study of Everolimus for Recurrent or Progressive Low-grade Gliomas in Children (NCT NCT01734512)

Last Updated: 2025-09-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2025-09-09

Participant Flow

Participant milestones

Participant milestones
Measure	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 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. Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
Overall Study STARTED	65
Overall Study COMPLETED	65
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus n=65 Participants 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. Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
Age, Customized 3-9 years old	35 Participants n=5 Participants
Age, Customized 10-21 years old	30 Participants n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	36 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	47 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	14 Participants n=5 Participants
Region of Enrollment United States	65 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 months

Outcome measures

Outcome measures
Measure	Everolimus n=65 Participants 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. Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
Percentage of Participants With Progression Free Survival at 6 Months	67 percentage Interval 54.0 to 77.0

SECONDARY outcome

Timeframe: Up to 6 months

The proportion of participants who demonstrated a complete or partial response as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1 Criteria where Complete Response (CR) is defined as the complete disappearance of all known disease for \>=8 weeks. Complete response is dated from time all lesions have disappeared on a stable or decreasing dose of corticosteroids. A Partial Response (PR) is a reduction of at least 50% in the size of all measurable tumor as quantitated by sum of the products of the largest diameters (SLD) of measurable lesions and maintained for \>=8 weeks on a stable or decreasing dose of corticosteroids. Partial response is dated from the time of first observation. Overall response also takes into account the response in both the target and non-target lesion, and the appearance of new lesions, where applicable and depend on the achievement of both measurement and confirmation criteria.

Outcome measures

Outcome measures
Measure	Everolimus n=65 Participants 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. Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
Proportion of Participants With Objective Response	0.05 proportion of participants

SECONDARY outcome

Timeframe: Up to 5 years

Progression free survival will be calculated from date of first treatment to the date of first observation of progressive disease, non-reversible neurological progression or increasing steroid requirements (applies to stable disease only), death due to any cause, or early discontinuation of treatment

Outcome measures

Outcome measures
Measure	Everolimus n=65 Participants 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. Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
Median Progression Free Survival in Recurrent Pediatric Low-grade Glioma (LGGs)	365 days Interval 225.0 to 765.0

SECONDARY outcome

Timeframe: Up to 5 years

Overall survival in participants with recurrent pediatric low-grade glioma (LGGs) will be calculated from date of original diagnoses to death using Kaplan Meier method. Median time to death and 95% confidence interval will be reported.

Outcome measures

Outcome measures
Measure	Everolimus n=65 Participants 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. Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
Median Overall Survival From Time of Diagnosis	NA days Less than 50% of the participants died at the time study data collection ended, so a median survival time could not be calculated due to the insufficient number of events.

SECONDARY outcome

Timeframe: Up to 5 years

Population: Less than 50% of the participants died at the time study data collection ended, so a median survival time could not be calculated due to the insufficient number of events.

Overall survival in participants with recurrent pediatric low-grade glioma (LGGs) will be calculated from date of study registration to death using Kaplan Meier method. Median time to death and 95% confidence interval will be reported.

Outcome measures

Outcome measures
Measure	Everolimus n=65 Participants 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. Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
Median Overall Survival From Time of Enrollment	NA days Less than 50% of the participants died at the time study data collection ended, so a median survival time could not be calculated as the curve did not drop below the level of detection.

Adverse Events

Everolimus

Serious events: 20 serious events

Other events: 62 other events

Deaths: 9 deaths

Serious adverse events

Serious adverse events
Measure	Everolimus n=65 participants at risk 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. Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
General disorders Edema face	1.5% 1/65 • Number of events 1 • Up to 5 years
Ear and labyrinth disorders Hearing Impaired	1.5% 1/65 • Number of events 1 • Up to 5 years
Nervous system disorders Seizure	3.1% 2/65 • Number of events 2 • Up to 5 years
Nervous system disorders Cognitive disturbance	1.5% 1/65 • Number of events 1 • Up to 5 years
Infections and infestations Sepsis	1.5% 1/65 • Number of events 1 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.5% 1/65 • Number of events 1 • Up to 5 years
Nervous system disorders Hydrocephalus	9.2% 6/65 • Number of events 12 • Up to 5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	3.1% 2/65 • Number of events 3 • Up to 5 years
Skin and subcutaneous tissue disorders Skin infection	3.1% 2/65 • Number of events 2 • Up to 5 years
Metabolism and nutrition disorders Dehydration	3.1% 2/65 • Number of events 2 • Up to 5 years
Nervous system disorders Encephalopathy	1.5% 1/65 • Number of events 1 • Up to 5 years
Nervous system disorders Headache	3.1% 2/65 • Number of events 5 • Up to 5 years
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other	3.1% 2/65 • Number of events 5 • Up to 5 years
Vascular disorders Hypertension	1.5% 1/65 • Number of events 1 • Up to 5 years
General disorders Fever	3.1% 2/65 • Number of events 2 • Up to 5 years
Surgical and medical procedures Surgical and medical procedures - Other	1.5% 1/65 • Number of events 1 • Up to 5 years
Gastrointestinal disorders Vomiting	1.5% 1/65 • Number of events 3 • Up to 5 years
Metabolism and nutrition disorders Hypernatremia	1.5% 1/65 • Number of events 1 • Up to 5 years
Infections and infestations Catheter related infection	1.5% 1/65 • Number of events 1 • Up to 5 years
Infections and infestations Infections and infestations - Other	1.5% 1/65 • Number of events 1 • Up to 5 years

Other adverse events

Other adverse events
Measure	Everolimus n=65 participants at risk 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. Everolimus: Everolimus tablet will be taken daily by mouth with water. All patients will be given a dose of 5 mg/m2/dose daily.
Investigations Cholesterol high	52.3% 34/65 • Number of events 63 • Up to 5 years
Investigations Aspartate aminotransferase increased	46.2% 30/65 • Number of events 62 • Up to 5 years
Investigations Alanine aminotransferase increased	40.0% 26/65 • Number of events 60 • Up to 5 years
Investigations Neutrophil count decreased	29.2% 19/65 • Number of events 41 • Up to 5 years
Investigations Lymphocyte count decreased	23.1% 15/65 • Number of events 25 • Up to 5 years
Investigations White blood cell decreased	23.1% 15/65 • Number of events 49 • Up to 5 years
Investigations Platelet count decreased	21.5% 14/65 • Number of events 23 • Up to 5 years
Investigations Investigations - Other	16.9% 11/65 • Number of events 27 • Up to 5 years
Investigations Weight loss	9.2% 6/65 • Number of events 8 • Up to 5 years
Investigations Alkaline phosphatase increased	9.2% 6/65 • Number of events 7 • Up to 5 years
Investigations Creatinine increased	6.2% 4/65 • Number of events 8 • Up to 5 years
Gastrointestinal disorders Mucositis oral	53.8% 35/65 • Number of events 94 • Up to 5 years
Gastrointestinal disorders Diarrhea	23.1% 15/65 • Number of events 30 • Up to 5 years
Gastrointestinal disorders Nausea	21.5% 14/65 • Number of events 16 • Up to 5 years
Gastrointestinal disorders Vomiting	16.9% 11/65 • Number of events 12 • Up to 5 years
Gastrointestinal disorders Oral pain	12.3% 8/65 • Number of events 11 • Up to 5 years
Gastrointestinal disorders Abdominal pain	10.8% 7/65 • Number of events 8 • Up to 5 years
Gastrointestinal disorders Gastrointestinal disorders - Other	7.7% 5/65 • Number of events 6 • Up to 5 years
Gastrointestinal disorders Stomach pain	6.2% 4/65 • Number of events 7 • Up to 5 years
Metabolism and nutrition disorders Hypertriglyceridemia	52.3% 34/65 • Number of events 98 • Up to 5 years
Metabolism and nutrition disorders Hyperglycemia	24.6% 16/65 • Number of events 30 • Up to 5 years
Metabolism and nutrition disorders Hypophosphatemia	23.1% 15/65 • Number of events 23 • Up to 5 years
Metabolism and nutrition disorders Hypokalemia	20.0% 13/65 • Number of events 35 • Up to 5 years
Metabolism and nutrition disorders Anorexia	13.8% 9/65 • Number of events 12 • Up to 5 years
Metabolism and nutrition disorders Hypernatremia	13.8% 9/65 • Number of events 18 • Up to 5 years
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other	9.2% 6/65 • Number of events 10 • Up to 5 years
Metabolism and nutrition disorders Hypomagnesemia	7.7% 5/65 • Number of events 7 • Up to 5 years
Metabolism and nutrition disorders Hypercalcemia	6.2% 4/65 • Number of events 4 • Up to 5 years
Metabolism and nutrition disorders Hyponatremia	6.2% 4/65 • Number of events 11 • Up to 5 years
Nervous system disorders Headache	32.3% 21/65 • Number of events 35 • Up to 5 years
Nervous system disorders Dizziness	7.7% 5/65 • Number of events 5 • Up to 5 years
General disorders Fatigue	38.5% 25/65 • Number of events 36 • Up to 5 years
General disorders Fever	15.4% 10/65 • Number of events 19 • Up to 5 years
General disorders Pain	6.2% 4/65 • Number of events 4 • Up to 5 years
Skin and subcutaneous tissue disorders Rash maculo-papular	18.5% 12/65 • Number of events 17 • Up to 5 years
Skin and subcutaneous tissue disorders Dry skin	7.7% 5/65 • Number of events 5 • Up to 5 years
Skin and subcutaneous tissue disorders Rash acneiform	7.7% 5/65 • Number of events 5 • Up to 5 years
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other	7.7% 5/65 • Number of events 5 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Cough	10.8% 7/65 • Number of events 9 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Sore throat	10.8% 7/65 • Number of events 10 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Epistaxis	9.2% 6/65 • Number of events 7 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Nasal congestion	7.7% 5/65 • Number of events 6 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	4.6% 3/65 • Number of events 4 • Up to 5 years
Blood and lymphatic system disorders Anemia	27.7% 18/65 • Number of events 47 • Up to 5 years
Infections and infestations Upper respiratory infection	12.3% 8/65 • Number of events 9 • Up to 5 years
Musculoskeletal and connective tissue disorders Pain in extremity	6.2% 4/65 • Number of events 5 • Up to 5 years
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	6.2% 4/65 • Number of events 5 • Up to 5 years
Cardiac disorders Sinus tachycardia	12.3% 8/65 • Number of events 17 • Up to 5 years
Vascular disorders Hypertension	9.2% 6/65 • Number of events 15 • Up to 5 years

Additional Information

Dr. Sabine Mueller, MD, PhD

University of California, San Francisco

Phone: (415) 502-7301

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place