Pediatric Recurrent/Refractory BRAFV600E-mutant GliomasEarly Phase 1NCT01748149
Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E (BRAFV600E)-Mutant Gliomas
A Early Phase 1 study testing Vemurafenib in people with Pediatric Recurrent/Refractory BRAFV600E-mutant Gliomas, run by University of California, San Francisco at 21 sites in 2 countries.
Trial summary
This is a multicenter, safety and pharmacokinetic trial to determine the MTD and/or select a recommended phase 2 dose (RP2D) of vemurafenib in children with recurrent or refractory gliomas containing the BRAFV600E or BRAF Ins T mutation. Read more about this study
- Who is it for?
- Ages Up to 25 years
- Conditions the study is for
- Pediatric Recurrent/Refractory BRAFV600E-mutant Gliomas
- What is being tested?
- Vemurafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 21 sitesin 2 countries
- Study dates
- 29 Apr 2014to 31 Jul 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with histologically confirmed diagnosis of glioma (WHO Grades I-IV) will be eligible. Patient tumors must test positive for the BRAFV600E mutation at University of California, San Francisco (UCSF) Molecular Pathology central laboratory. If mutation cannot be confirmed from a prior test and archival tumor is not available to confirm presence of BRAFV600E mutation, patients must have tumor biopsy to collect tumor sample for mutation confirmation.
- Patient must be less than 18 years of age at registration for the safety study. Patients must be < 25 years of age for Phase 0 and Efficacy Cohorts.
- Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
- Patients must be able to swallow tablets (or applesauce, if part of bioavailability "crushed" six patient cohort).
- Patient must have magnetic resonance (MR) imaging performed within two weeks of first dose of drug.
- Karnofsky Performance Scale (KPS for > 16 yrs of age) or Lansky Performance Score(LPS for ≤ 16 years of age) ≥ 60 assessed within two weeks prior to registration.
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- The patient must have failed at least one prior therapy besides surgery- radiation or chemotherapy (either cytotoxic or biologic agent)- prior to study registration. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks if nitrosourea.
- Biologic agent: Patient must have recovered from any toxicity potentially related to the agent and received their last dose of the biologic agent ≥ 7 days prior to study registration.
- For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
- For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the study chair prior to registration.
- Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration. Such patients should be discussed with the study chair prior to registration.
- Radiation: Patients must have:
- Had their last fraction of local irradiation to primary tumor ≥12 weeks prior to registration; investigators are reminded to review potentially eligible cases to avoid confusion with pseudo-progression.
- Had their last fraction of craniospinal irradiation or total body irradiation > 12 weeks prior to registration
- Bone Marrow Transplant: Patient must be:
- ≥ 6 months since allogeneic bone marrow transplant prior to registration
- ≥ 3 months since autologous bone marrow/stem cell prior to registration
- Corticosteroids: Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to registration.
- Growth factors: Off all colony forming growth factor(s) for at least 1 week prior to registration (filgrastim, sargramostim, erythropoietin) and at least 2 weeks for long- acting formulations.
- Organ Function: Documented within 14 days of registration and within 7 days of the start of treatment.
- Adequate bone marrow function:
- Absolute neutrophil count ≥ 1000/μl (unsupported)
- Platelets ≥ 75,000/μl (unsupported)
- Hemoglobin ≥ 8 g/dL (may be supported)
- Adequate hepatic function:
- Total bilirubin < 1.5 times upper limit of normal for age
- serum glutamate pyruvate transaminase (SGPT)/serum glutamate oxaloacetate transaminase (SGOT) (ALT/AST) ≤ 2.5 times institutional upper limit of normal for age
- Adequate renal function:
- Creatinine clearance or Radioisotope glomerular filtration rate (GFR) ≥ 70 ml/min/1.73m2 or a serum creatinine based on age as follows: Less than or equal to 5 years of age= Maximum Serum Creatinine (mg/dL)of 0.8; Older than 5 but 10 years or younger= Maximum Serum Creatinine (mg/dL)of 1.0; Older than 10 but 15 years or younger= Maximum Serum Creatinine (mg/dL)of 1.2; Older than 15 years= Maximum Serum Creatinine (mg/dL) of 1.5
- Electrolytes:
- Sodium: ≥ 130 and ≤ 145 mmol/L
- Potassium: 3.4- 4.8 mmol/L
- Calcium: ≥ 7 mg/dL
- Magnesium: ≥ 0.7 mmol/L
- Nutrition:
- Albumin ≥ 3 g/dL
- Cardiac:
- Corrected QT (QTc) interval <450 msec on EKG.
- Female patients of childbearing potential must not be pregnant or breast-feeding. Female patients of childbearing potential must have a negative serum or urine pregnancy test. The effects of Vemurafenib on the developing human fetus are unknown. For this reason, 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, and for four weeks after dosing with vemurafenib ceases. Women must refrain from donating eggs during this same period. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 weeks after completion of study drug administration.
- All skin lesions suspicious for keratoacanthomas/cutaneous squamous cell carcinoma (cSCC) found at baseline dermatology visit must have been excised.
- Signed informed consent according to institutional guidelines must be obtained.
- Specific inclusion criteria for Pre-Surgical Cohort:
- Patients under 25 years of age will be eligible for the pre-surgical cohort. Patients between 18-25 years of age will be treated at the adult FDA-approved dose of 960 mg BID and can be enrolled immediately. Patients less than 18 years of age will be enrolled and treated at the pediatric MTD once it is defined in the Safety Cohort.
- Surgical patients must have tumor that needs to be removed/debulked and is accessible for the neurosurgeon. Need for surgery must be such that the patient can take drug for 10 days before surgery.
- Specific inclusion criteria for Expansion cohort:
- Expansion cohort will be open if tissue drug levels in the Pre-Surgical cohort meet criteria (Tumor tissue drug concentration is greater than 50 nM). Patients under 25 years of age will be eligible for the expansion cohort. Patients between 18 and 25 years of age will take adult dose of 960 mg BID. Patients less than 18 years of age will take the MTD defined in the safety cohort.
Who cannot join
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that will likely interfere with the study procedures or results.
- All patients with known clinical diagnosis of Neurofibromatosis Type 1 are excluded.
- Patients receiving any other anticancer or investigational drug therapy.
- Patients with uncontrolled seizures are not eligible for the study.
- Previous BRAF inhibitor use such as vemurafenib, GSK2118436 or sorafenib.
- Patients with QTc interval >450 msecs or other factors that increase the risk of QTprolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) including heart failure that meets New York Heart Association(NYHA) class III and IV definitions are excluded.
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- Required use of a concomitant medication that can prolong the QT interval. A comprehensive list of agents with the potential to cause QTc prolongation can be found at http://www.azcert.org/medical-pros/drug-lists/browse-drug-list.cfm?alpha=A
- Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vemurafenib.
- Negative result of BRAFV600E screening test performed at UCSF.
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United States20 sites
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610
Texas Children's Hospital
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
Mattel Children's Hospital UCLA
Los Angeles, California, 90095
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
University of Minnesota/Masonic Children's Hospital
Minneapolis, Minnesota, 55454
Children's Hospital and Research Center at Oakland
Oakland, California, 94609-1809
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University
Portland, Oregon, 97239
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Rady Children's Hospital - San Diego
San Diego, California, 92123
UCSF Medical Center-Mount Zion
San Francisco, California, 94115
UCSF Medical Center-Parnassus
San Francisco, California, 94143
Seattle Children's Hospital
Seattle, Washington, 98105
Saint Louis Children's Hospital
St Louis, Missouri, 63110
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Pediatric Neuro-Oncology Consortium (PNOC)-002: Safety, Phase 0, and Pilot Efficacy Study of Vemurafenib, an Oral Inhibitor of BRAFV600E, in Children and Young Adults With Recurrent/Refractory BRAFV600E- or BRAF Ins T Mutant Brain Tumors
This is a multicenter, safety and pharmacokinetic trial to determine the MTD and/or select a recommended phase 2 dose (RP2D) of vemurafenib in children with recurrent or refractory gliomas containing the BRAFV600E or BRAF Ins T mutation.
Read the detailed description
This is a multicenter, safety and pharmacokinetic trial to determine the MTD and/or select a recommended phase 2 dose (RP2D) of vemurafenib in children with recurrent or refractory gliomas containing the BRAFV600E or BRAF Ins T mutation. Using the RP2D, the study team will then conduct a Phase 0 study in a pre-surgical cohort of 10 patients requiring debulking surgery at the time of recurrence. These patients will receive neo-adjuvant vemurafenib, thus allowing the study team to measure intra-tumoral drug concentrations and target inhibition. An expansion cohort will then be enrolled to allow the study team to preliminarily estimate efficacy. Participants are followed up for adverse events while receiving study treatment until resolution.
- Being tested
- Vemurafenib
- Keywords
- recurrent/refractory BRAFV600E-mutant gliomas, pediatrics, children, neo-adjuvant vemurafenib
- Medical subject headings
- Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VemurafenibDrug
Also called RO5185426, PLX4032
Vemurafenib is supplied in 120-mg and 240-mg film-coated tablets packed in bottles for oral administration. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. The dose prescribed should be rounded to the nearest deliverable dose based on the BSA adjustment and the available pill sizes. Dosing will not exceed the adult MTD of 960 mg twice a day (BID). Patients will be provided with a Medication Diary for vemurafenib, instructed in its use, and asked to bring the diary with them to each appointment.
Treatment will be administered on an outpatient basis. Dosing is based on the BSA calculated at the beginning of each course of therapy. The dose prescribed should be rounded to the nearest deliverable dose based on the BSA adjustment and the available pill sizes. Regardless of cohort, patients will self-administer vemurafenib BID at the assigned dose level. Patients will be instructed to hold their dose of vemurafenib for PK or surgery.
| Study group | Role | What they receive |
|---|---|---|
| Vemurafenib | Experimental | Vemurafenib should be swallowed whole with 8 oz (1 cup) of water. Pharmacokinetic studies will determine if vemurafenib can be "crushed". If patients receiving "crushed" tablets are felt to receive adequate exposure, then they will be allowed to participate in the expansion cohort. [Patients approved to take "crushed" tablets should use a pill crusher and mix pill with 3-5 ml apple sauce]. If not, then only patients able to swallow whole pills will be eligible.
The patient will be requested to maintain a medication diary of each dose of medication. The medication diary will be returned to clinic staff at the end of each cycle. Receives: Drug: Vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D)
To determine if the maximum tolerated dose of vemurafenib established in adults is safe and tolerable in pediatric patients with BRAFV600E-mutant gliomas. (Dose is adjusted for pediatric use. Weighted dose extrapolated from FDA approved standard adult dose)
Measured: Up to 4 weeks
Proportion of participants with dose limiting toxicities
To describe the toxicity profile/dose limiting toxicity (DLT) of vemurafenib in children with recurrent or refractory glioma. DLT will be assessed by monitoring for adverse events, scheduled laboratory assessments, vital sign measurements, ECGs, and physical examinations. The severity of the toxicities will be graded according to the NCI CTCAE v 4.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity and relationship to study drug. Safety will be assessed weekly for the first 4 weeks and then every 4 weeks. Descriptive statistics will be utilized to display the data on toxicity seen.
Safety will be assessed weekly for the first 4 weeks and then every 4 weeks. Descriptive statistics will be utilized to display the data on toxicity seen.
Measured: Up to 4 weeks
Median concentrations of vemurafenib in the blood found through pharmacokinetic (PK) samples
Venous blood samples (2 mL) will be collected in sodium heparin to measure concentrations of vemurafenib for each PK blood collection.
To characterize the pharmacokinetics of vemurafenib in pediatric patients. Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form. Mandatory plasma pharmacokinetic studies will be performed in all patients enrolled on the MTD, pre-surgical, and "crushed" pill cohorts of this trial. Because the pharmacokinetics of this agent are unknown in the pediatric population, this information will be essential for evaluating toxicity and disease response and for refining dosing in future clinical trials of vemurafenib.
Measured: Up to 4 weeks
Objective Response Rate
To document antitumor activity of treatment with vemurafenib, as measured by objective responses.Objective response will be assessed using the RECIST Response criteria. The response will be collected on case report forms (CRFs). The study team will include complete responses (CR's), partial responses (PR's) and sustained stable disease (SSD- defined as stable disease on two successive scans). The target response rate is 20%. The number and percent of subjects with each type of response will be summarized and presented in data listings.
Measured: Up to 4 weeks
Secondary outcomes (2)
Median Intra-tumoral drug level concentration
Subsequent to the safety cohort, the study team will begin enrollment into a presurgical study. Patients who are candidates for surgical resection at the time of relapse, would be eligible for this component of the trial. The aim will be to measure drug levels (based on the dose chosen in the safety cohort) in tumor, with an additional aim to describe target modulation, with vemurafenib treated tumor compared with corresponding archived tissue from prior surgery. Tumor phospho-extracellular signal-regulated kinase (ERK) levels will be used as a molecular readout for agent activity. Drug levels will be measured by liquid chromatography/Mass spec. The statistical analysis will be descriptive and will be limited to frequency tables and summary statistics.
Measured: Up to 4 weeks
Progression-free survival
Progression-free survival at 6 months (PFS6) is defined as the proportion of patients alive and progression-free 180 days after Study Day 1. Duration of PFS is defined as the time from Study Day 1 to the earlier of disease progression or death due to any cause. All patients included in the study must be assessed for PFS6, even if there are major protocol treatment deviations or if they are ineligible.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2012 (estimated)
- Study start29 Apr 2014
- Primary completion5 Dec 2018
- Study completion31 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pediatric Recurrent/Refractory BRAFV600E-mutant GliomasStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Sabine Mueller, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01748149
- Sponsor's protocol ID
- 120819
- Other IDs
- NCI-2014-00387
- Status last verified
- Jul 2025
- First submitted
- 7 Dec 2012
- Last updated
- 3 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nicolaides T, Nazemi KJ, Crawford J, Kilburn L, Minturn J, Gajjar A, Gauvain K, Leary S, Dhall G, Aboian M, Robinson G, Long-Boyle J, Wang H, Molinaro AM, Mueller S, Prados M. Phase I study of vemurafenib in children with recurrent or progressive BRAFV600E mutant brain tumors: Pacific Pediatric Neuro-Oncology Consortium study (PNOC-002). Oncotarget. 2020 May 26;11(21):1942-1952. doi: 10.18632/oncotarget.27600. eCollection 2020 May 26.
PubMed 32523649
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pediatric Neuro-Oncology Consortium (PNOC)-002: Safety, Phase 0, and Pilot Efficacy Study of Vemurafenib, an Oral Inhibitor of BRAFV600E, in Children and Young Adults With Recurrent/Refractory BRAFV600E- or BRAF Ins T Mutant Brain Tumors
- ClinicalTrials.gov ID
- NCT01748149
- Acronym / sponsor ID
- 120819
- Keywords
- recurrent/refractory BRAFV600E-mutant gliomas, pediatrics, children, neo-adjuvant vemurafenib
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- 29 Apr 2014 (actual)
- Primary completion
- 5 Dec 2018 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 12 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, safety and pharmacokinetic trial to determine the MTD and/or select a recommended phase 2 dose (RP2D) of vemurafenib in children with recurrent or refractory gliomas containing the BRAFV600E or BRAF Ins T mutation.
Detailed description
This is a multicenter, safety and pharmacokinetic trial to determine the MTD and/or select a recommended phase 2 dose (RP2D) of vemurafenib in children with recurrent or refractory gliomas containing the BRAFV600E or BRAF Ins T mutation. Using the RP2D, the study team will then conduct a Phase 0 study in a pre-surgical cohort of 10 patients requiring debulking surgery at the time of recurrence. These patients will receive neo-adjuvant vemurafenib, thus allowing the study team to measure intra-tumoral drug concentrations and target inhibition. An expansion cohort will then be enrolled to allow the study team to preliminarily estimate efficacy. Participants are followed up for adverse events while receiving study treatment until resolution.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vemurafenib | Experimental | Drug: VemurafenibVemurafenib should be swallowed whole with 8 oz (1 cup) of water. Pharmacokinetic studies will determine if vemurafenib can be "crushed". If patients receiving "crushed" tablets are felt to receive adequate exposure, then they will be allowed to participate in the expansion cohort. [Patients approved to take "crushed" tablets should use a pill crusher and mix pill with 3-5 ml apple sauce]. If not, then only patients able to swallow whole pills will be eligible. The patient will be requested to maintain a medication diary of each dose of medication. The medication diary will be returned to clinic staff at the end of each cycle. |
Who may qualify
- Ages
- Up to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (47 listed)
- Patients with histologically confirmed diagnosis of glioma (WHO Grades I-IV) will be eligible. Patient tumors must test positive for the BRAFV600E mutation at University of California, San Francisco (UCSF) Molecular Pathology central laboratory. If mutation cannot be confirmed from a prior test and archival tumor is not available to confirm presence of BRAFV600E mutation, patients must have tumor biopsy to collect tumor sample for mutation confirmation.
- Patient must be less than 18 years of age at registration for the safety study. Patients must be < 25 years of age for Phase 0 and Efficacy Cohorts.
- Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
- Patients must be able to swallow tablets (or applesauce, if part of bioavailability "crushed" six patient cohort).
- Patient must have magnetic resonance (MR) imaging performed within two weeks of first dose of drug.
Key exclusion criteria (10 listed)
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) that will likely interfere with the study procedures or results.
- All patients with known clinical diagnosis of Neurofibromatosis Type 1 are excluded.
- Patients receiving any other anticancer or investigational drug therapy.
- Patients with uncontrolled seizures are not eligible for the study.
- Previous BRAF inhibitor use such as vemurafenib, GSK2118436 or sorafenib.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VemurafenibAlso: RO5185426, PLX4032Vemurafenib is supplied in 120-mg and 240-mg film-coated tablets packed in bottles for oral administration. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. The dose prescribed should be rounded to the nearest deliverable dose based on the BSA adjustment and the available pill sizes. Dosing will not exceed the adult MTD of 960 mg twice a day (BID). Patients will be provided with a Medication Diary for vemurafenib, instructed in its use, and asked to bring the diary with them to each appointment. Treatment will be administered on an outpatient basis. Dosing is based on the BSA calculated at the beginning of each course of therapy. The dose prescribed should be rounded to the nearest deliverable dose based on the BSA adjustment and the available pill sizes. Regardless of cohort, patients will self-administer vemurafenib BID at the assigned dose level. Patients will be instructed to hold their dose of vemurafenib for PK or surgery. | Drug | Vemurafenib |
Primary outcome
Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D)
Time frame: Up to 4 weeks
To determine if the maximum tolerated dose of vemurafenib established in adults is safe and tolerable in pediatric patients with BRAFV600E-mutant gliomas. (Dose is adjusted for pediatric use. Weighted dose extrapolated from FDA approved standard adult dose)
Proportion of participants with dose limiting toxicities
Time frame: Up to 4 weeks
To describe the toxicity profile/dose limiting toxicity (DLT) of vemurafenib in children with recurrent or refractory glioma. DLT will be assessed by monitoring for adverse events, scheduled laboratory assessments, vital sign measurements, ECGs, and physical examinations. The severity of the toxicities will be graded according to the NCI CTCAE v 4.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity and relationship to study drug. Safety will be assessed weekly for the first 4 weeks and then every 4 weeks. Descriptive statistics will be utilized to display the data on toxicity seen. Safety will be assessed weekly for the first 4 weeks and then every 4 weeks. Descriptive statistics will be utilized to display the data on toxicity seen.
Median concentrations of vemurafenib in the blood found through pharmacokinetic (PK) samples
Time frame: Up to 4 weeks
Venous blood samples (2 mL) will be collected in sodium heparin to measure concentrations of vemurafenib for each PK blood collection. To characterize the pharmacokinetics of vemurafenib in pediatric patients. Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form. Mandatory plasma pharmacokinetic studies will be performed in all patients enrolled on the MTD, pre-surgical, and "crushed" pill cohorts of this trial. Because the pharmacokinetics of this agent are unknown in the pediatric population, this information will be essential for evaluating toxicity and disease response and for refining dosing in future clinical trials of vemurafenib.
Objective Response Rate
Time frame: Up to 4 weeks
To document antitumor activity of treatment with vemurafenib, as measured by objective responses.Objective response will be assessed using the RECIST Response criteria. The response will be collected on case report forms (CRFs). The study team will include complete responses (CR's), partial responses (PR's) and sustained stable disease (SSD- defined as stable disease on two successive scans). The target response rate is 20%. The number and percent of subjects with each type of response will be summarized and presented in data listings.
2 secondary outcomes
Median Intra-tumoral drug level concentration
Time frame: Up to 4 weeks
Progression-free survival
Time frame: Up to 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2025.
- Derived from this study: PubMed 32523649Nicolaides T, Nazemi KJ, Crawford J, Kilburn L, Minturn J, Gajjar A, Gauvain K, Leary S, Dhall G, Aboian M, Robinson G, Long-Boyle J, Wang H, Molinaro AM, Mueller S, Prados M. Phase I study of vemurafenib in children with recurrent or progressive BRAFV600E mutant brain tumors: Pacific Pediatric Neuro-Oncology Consortium study (PNOC-002). Oncotarget. 2020 May 26;11(21):1942-1952. doi: 10.18632/oncotarget.27600. eCollection 2020 May 26.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sabine Mueller, MD principal investigator
University of California, San Francisco
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Vemurafenib in people with Pediatric Recurrent/Refractory BRAFV600E-mutant Gliomas, run by University of California, San Francisco at 21 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 47 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D) (time frame: Up to 4 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01748149, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2025.