Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E (BRAFV600E)-Mutant Gliomas

Completed · Early Phase 1

Conditions studied: Pediatric Recurrent/Refractory BRAFV600E-mutant Gliomas

In brief

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.

Key facts

Study ID

NCT01748149

Run by

University of California, San Francisco

People needed

40

Starts

2014-04-29

Expected to finish

2025-07-31

Last updated by the study team

2025-08-03

Who can join

Age: any, up to 25. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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)

You may not qualify if…

• 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.
• 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.

Where it is running

• Children's Hospital Los Angeles — Los Angeles, California, United States
• Mattel Children's Hospital UCLA — Los Angeles, California, United States
• Children's Hospital and Research Center at Oakland — Oakland, California, United States
• Rady Children's Hospital - San Diego — San Diego, California, United States
• UCSF Medical Center-Mount Zion — San Francisco, California, United States
• UCSF Medical Center-Parnassus — San Francisco, California, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• University of Florida Health Science Center - Gainesville — Gainesville, Florida, United States
• Lurie Children's Hospital-Chicago — Chicago, Illinois, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States
• University of Minnesota/Masonic Children's Hospital — Minneapolis, Minnesota, United States
• Saint Louis Children's Hospital — St Louis, Missouri, United States
• Nationwide Children's Hospital — Columbus, Ohio, United States
• Oregon Health and Science University — Portland, Oregon, United States
• Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States
• St. Jude Children's Research Hospital — Memphis, Tennessee, United States
• Texas Children's Hospital — Houston, Texas, United States
• Huntsman Cancer Institute/University of Utah — Salt Lake City, Utah, United States
• Seattle Children's Hospital — Seattle, Washington, United States
• Hospital for Sick Children — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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