Clinical trial NCT03593993: A Biospecimen Collection Study in BRAF-V600E Mutated Recurrent Gliomas
Official title: A Biospecimen Collection Study to Evaluate the Pharmacokinetic, Pharmacodynamic, and Resistance Profile to Trametinib and Dabrafenib in BRAF-V600E Mutated Recurrent Gliomas
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Glioma
BRAF V600E
Pleomorphic Xantho-Astrocytoma
Glioblastoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Musella Foundation
First posted: 2018-07-20
Enrollment: 3
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with primary brain tumors who are taking dabrafenib and/or trametinib and are going to have a surgical resection.

Brief summary: This is a surgical biospecimen collection study. The purpose of this study is to understand how much of two drugs (dabrafenib and trametinib) are able to penetrate brain tumors and turn off the RAF signaling pathway. This is important because these drugs are currently FDA approved for other tumors and may have efficacy in brain tumors with the BRAF V600E mutation.

Detailed description: The primary goal of this study is to establish concentrations of dabrafenib and trametinib in enhancing brain tissue and cerebrospinal fluid from people with BRAF-V600E mutant recurrent gliomas who undergo tumor resection. The exploratory goals are to measure the amount of ERK signaling pathway activity, to identify mechanisms of resistance to these drugs, and evaluate feasibility of measuring tumor DNA in cerebrospinal fluid.

People (adults or children) with brain tumors who are already taking dabrafenib and / or trametinib and are in need of a surgical resection are potentially eligible. On the day of surgery, blood, cerebrospinal fluid, and tumor tissue will be collected for research purposes.

Eligibility criteria: Inclusion Criteria:

* Subjects must have a history of primary brain tumor (including but not limited to glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic ganglioglioma (AG), and anaplastic pleomorphic xanthoastrocytoma (PXA)).
* Subjects must have a BRAF-V600 mutation identified in previous tissue analysis (may be IHC or PCR based). Allowable mutations include V600E, V600K, V600R, and V600D.
* Subjects must be taking dabrafenib at a dose of at least 50mg twice daily (adults only) and / or trametinib at a dose of at least 1mg daily (adults only) for at least 7 days prior to surgery as prescribed by their treating physician. Note: Pediatric patients may be taking any dose of dabrafenib and / or trametinib as prescribed by their treating physician for at least 7 days prior to surgery.
* Subjects must be undergoing surgery for clinical purposes.
* Written informed consent - a signed informed consent and/or assent (as age appropriate) for study participation will be obtained according to institutional guidelines.

Exclusion Criteria:

* Subjects who are receiving any other investigational agents or chemotherapeutic agents.
* Subjects for whom collection of blood, spinal fluid, or tissue samples is unsafe or clinically inadvisable.

Primary outcomes:
measure: Concentration of dabrafenib in brain tumor
timeFrame: Day 1
measure: Concentration of trametinib in brain tumor
timeFrame: Day 1
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusettes General Hospital
state: Massachusetts
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Stuart Grossman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins School of Medicine
name: Karisa Schreck, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: