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Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E (BRAFV600E)-Mutant Gliomas | Clinical Trials | Clareo Health

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

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

NCT01748149•University of California, San Francisco

View on ClinicalTrials.gov

Summary

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.

Eligibility

Age

0 - 25 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•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.
+35 more criteria

Exclusion Criteria

•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.
•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.

Locations (21)

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

Key Dates

Start Date

April 29, 2014

Primary Completion Date

December 5, 2018

Completion Date

July 31, 2025

Last Updated

August 3, 2025

Enrollment

ACTUAL participants

Conditions

Pediatric Recurrent/Refractory BRAFV600E-mutant Gliomas

Interventions

Vemurafenib

DRUG