NCT02015117

Trametinib With or Without Whole Brain Radiation Therapy in Treating Patients With Brain Metastases

A Phase 1 Study of Trametinib in Combination With Radiation Therapy for Brain Metastases

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of trametinib with or without whole brain radiation therapy in treating patients with brain metastases. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs, such as trametinib, may make tumor cells more sensitive to radiation therapy. Giving trametinib with whole brain radiation therapy may be a better treatment for brain metastases.

Detailed description

PRIMARY OBJECTIVES: I. To identify the maximally tolerated dose of trametinib to be used in combination with whole brain radiation therapy in patients with brain metastases. (Cohort A) II. To quantify trametinib in resected brain metastatic lesions utilizing high performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) and compare to quantification of adjacent tissues: brain margin, arachnoid, and cerebrospinal fluid (CSF). (Cohort B) SECONDARY OBJECTIVES: I. To evaluate the tolerability and feasibility of the combination of trametinib and radiation therapy to brain for brain metastases. II. To evaluate the objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) criteria of combination trametinib and radiation therapy. III. To evaluate the local control rate, as measure from the time of study enrollment until the time of death. IV. To evaluate the neurologic progression-free survival, as measured from the time of study enrollment until the time of progression within the brain or death. V. To evaluate overall survival, as measured from the time of study enrollment until the time of death. TERTIARY OBJECTIVES: I. To quantify cyclin D1, p27, phosphorylated mitogen-activated protein kinase 1 (pERK)-1/2, phosphorylated v-akt murine thymoma viral oncogene homolog 1 (pAKT), phosphatase and tensin homolog gene (PTEN), phosphorylated mammalian target of rapamycin (pMTOR), phosphorylated ribosomal protein S6 kinase (pS6K), and ribosomal protein S6 (pS6) of resected metastatic brain lesions via quantitative immunohistochemistry (IHC) and compare to the IHC profile of the primary tumor. OUTLINE: This is a dose-escalation study of trametinib. Patients are assigned to 1 of 2 treatment cohorts. COHORT A: Patients receive trametinib orally (PO) once daily (QD) for 4 weeks. Beginning in week 2, patients undergo whole brain radiation therapy five days a week for 3 weeks. Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity. COHORT B: Patients receive trametinib PO QD on days 1-14 followed by surgical resection of the tumor. After completion of study treatment, patients are followed up for 4 weeks, every 2 months for 1 year, every 3 months for 3 years, and then every 6 months thereafter.

Conditions

• Metastatic Malignant Neoplasm in the Brain

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies
PROCEDURE	Therapeutic Conventional Surgery	Undergo surgical resection of the tumor
DRUG	Trametinib	Given PO
RADIATION	Whole-Brain Radiotherapy	Undergo whole-brain radiation therapy

Timeline

• Start date: 2014-04-28
• Primary completion: 2020-07-10
• Completion: 2026-10-08
• First posted: 2013-12-19
• Last updated: 2026-04-13

Locations

1 site across 1 country: United States