A Biospecimen Collection Study in BRAF-V600E Mutated Recurrent Gliomas

Glioblastoma Clinical Trial

Official title:

A Biospecimen Collection Study to Evaluate the Pharmacokinetic, Pharmacodynamic, and Resistance Profile to Trametinib and Dabrafenib in BRAF-V600E Mutated Recurrent Gliomas

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03593993
• Other study ID #: J1801
• Secondary ID: IRB00158788
• Status: Terminated
• Start date: May 19, 2018
• Est. completion date: July 7, 2023

Study information

• Verified date: October 2023
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: July 7, 2023
• Est. primary completion date: July 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Weeks and older

Eligibility

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.

Related Conditions & MeSH terms

• Astrocytoma
• BRAF V600E
• Glioblastoma
• Glioma
• Pleomorphic Xantho-Astrocytoma

Intervention

Procedure:
• Surgical Cohort
Blood, cerebrospinal fluid, and surgical tissue collected during procedure

Locations

Country	Name	City	State
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Massachusettes General Hospital	Boston	Massachusetts
United States	Penn State Hershey Medical Center	Hershey	Pennsylvania
United States	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Musella Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Concentration of dabrafenib in brain tumor	Obtain single time-point concentration of dabrafenib in enhancing brain tissue (ng/mL) using liquid chromatography/mass spectrometry with one single, random sample	Day 1
Primary	Concentration of trametinib in brain tumor	Obtain single time-point concentration of trametinib in enhancing brain tissue (ng/mL) using liquid chromatography/mass spectrometry with one single, random sample	Day 1