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

Running, not enrolling · Phase 1

Conditions studied: Metastatic Malignant Neoplasm in the Brain

In brief

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.

Key facts

Study ID

NCT02015117

Run by

National Cancer Institute (NCI)

People needed

10

Starts

2014-04-28

Expected to finish

2026-10-08

Last updated by the study team

2026-04-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically confirmed cancer with measurable or evaluable brain metastases by computed tomography (CT) or magnetic resonance imaging (MRI); MRI is preferred, but a CT scan is acceptable for patients that are unable to have an MRI
• Eastern Cooperative Oncology Group (ECOG) performance status 0 -1
• All prior treatment- related toxicities must be Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) =< grade 1 (except alopecia) at the time of enrollment
• Absolute neutrophil count >= 1.5 x 10\^9/L
• Hemoglobin >= 9 g/dL
• Platelets >= 100 x10\^9/L
• Prothrombin time (PT)/international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.5 x upper limit of normal (ULN) unless using warfarin for therapeutic anti-coagulation
• Albumin >= 2.5 g/dL
• Total bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Creatinine =< 1.5 ULN or calculated creatinine clearance >= 50 mL/min or 24-hour urine creatinine clearance >= 50 mL/min; calculated by the Cockcroft-Gault formula
• Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram (ECHO) or multigated acquisition scan (MUGA); same method as used at baseline must be use throughout the study, ECHO is the preferred method
• Life expectancy of at least 3 months in the opinion of investigator
• Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
• Women of child-bearing potential (WOCBP) must have a negative pregnancy test within 14 days prior to start of study treatment, and counselled on contraception/abstinence while receiving the study treatment; urine or serum human chorionic gonadotropin (HCG) is an acceptable pregnancy assessment; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; women of child-bearing potential must have a negative serum or urine pregnancy test within 14 days prior to randomization; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of trametinib administration

You may not qualify if…

• Prior radiation therapy to the whole brain (prior stereotactic radiosurgery or fractionated stereotactic radiation therapy to focal areas is allowed)
• Evidence of leptomeningeal metastases
• Urgent need of treatment to prevent acute neurologic deterioration
• Radiosensitive primary tumor such as small cell lung cancer, germ cell tumors, lymphoma, leukemia, or multiple myeloma
• History of another malignancy that makes determination of the source of the brain metastases uncertain
• History of interstitial lung disease or pneumonitis
• Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 14 days prior to enrollment and/or daily or weekly chemotherapy with the potential for delayed toxicity within 14 days prior to enrollment
• Use of other anti-cancer therapies within five half-lives from the previous dose of the prior anti-cancer therapy preceding enrollment and during the study
• Symptomatic or untreated spinal cord compression
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib, or excipients or to dimethyl sulfoxide (DMSO)
• Current use of a prohibited medication; the following medications or non-drug therapies are prohibited:
• Other anti-cancer therapy while on study treatment; (note: megestrol [Megace] if used as an appetite stimulant is allowed)
• Concurrent treatment with bisphosphonates is permitted; however, treatment must be initiated prior to enrollment; prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
• Concurrent use of all herbal supplements is prohibited during the study (including, but not limited to, St. John's wort, kava, ephedra [ma huang], gingko biloba, dehydroepiandrosterone [DHEA], yohimbe, saw palmetto, or ginseng)
• Drugs that potently inhibit or induce CYP3A4 should be administered with caution; below are a few examples of the agents:
• Drugs that may increase exposure of trametinib (CYP3A4 inhibitors):
• Antivirals: amprenavir, atazanavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir
• Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin
• Antifungals: fluconazole, itraconazole, ketoconazole, voriconazole
• Antidepressants: nefazodone
• Calcium channel blockers: mibefradil, diltiazem, verapamil
• Miscellaneous: aprepitant
• Drugs that may decrease exposure of trametinib (CYP3A4 inducers)
• Antivirals: efavirenz, nevirapine
• Antibiotic: rifampin

Where it is running

• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States

Full record on ClinicalTrials.gov

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