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MEK Inhibitor

Trametinib with/without Radiation for Brain Metastasis

Phase 1

Waitlist Available

Led By Joshua D Palmer

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

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

Must not have

History of another malignancy that makes determination of the source of the brain metastases uncertain

Unable to reliably be immobilized for safe administration of whole brain radiation therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the effects of a drug called trametinib, with or without radiation therapy, in patients with brain metastases. Trametinib may stop the growth of tumor cells by blocking enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving trametinib with radiation therapy may be a better treatment for brain metastases.

Who is the study for?

This trial is for patients with brain metastases who can swallow pills, have no significant gastrointestinal issues affecting drug absorption, and meet specific blood count requirements. They must not need urgent neurologic treatment, have a history of certain lung or heart conditions, or be on conflicting medications. Women must test negative for pregnancy and use contraception; men also agree to contraception.

What is being tested?

The study is testing the effects and optimal dosage of trametinib alone or combined with whole-brain radiation therapy in treating brain tumors. Trametinib blocks enzymes that promote tumor growth while radiation aims to kill tumor cells directly.

What are the potential side effects?

Potential side effects include skin rash, diarrhea, fatigue, swelling in parts of the body due to fluid retention (edema), shortness of breath, coughing up blood (hemoptysis), high blood pressure (hypertension), and decreased ejection fraction indicating potential heart problems.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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All my previous treatment side effects are mild, except for hair loss.

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My cancer has spread to my brain, confirmed by a CT or MRI scan.

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My blood tests for liver and kidney function are within normal ranges.

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I can take pills and don't have major stomach or bowel issues affecting drug absorption.

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I am fully active or can carry out light work.

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My heart pumps well, with an ejection fraction of 50% or higher.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had cancer before, making it unclear if my brain metastases come from a new or old cancer.

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I cannot stay still for brain radiation treatment.

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My cancer has spread to the lining of my brain and spinal cord.

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I need treatment urgently to prevent worsening of my neurological condition.

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I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

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I have had interstitial lung disease or pneumonitis.

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I haven't had major surgery or intense cancer treatment in the last 2 weeks.

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I have or am at risk for eye blood vessel blockage or retinal detachment.

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I have spinal cord compression that is causing symptoms or has not been treated.

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My cancer type is known to respond well to radiation therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Frequency of dose-limiting toxicities (DLT), defined as the maximum dose level of trametinib where at most 1 of 6 patients experience DLT (Cohort A)

Quantification of trametinib in resected brain metastatic lesions utilizing high performance liquid chromatography/tandem mass spectrometry (Cohort B)

Secondary study objectives

Local control rate

Neurologic progression-free survival

Objective response rate per Response Evaluation Criteria in Solid Tumors

+3 more

Other study objectives

Quantification of cyclin D1, p27, pERK-1/2, pAKT, PTEN, pMTOR, pS6K, and pS6 of resected metastatic brain lesions via immunohistochemistry

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Cohort B (trametinib, surgery)Experimental Treatment4 Interventions

Patients receive trametinib PO QD on days 1-14 followed by surgical resection of the tumor.

Group II: Cohort A (trametinib, whole-brain radiation therapy)Experimental Treatment4 Interventions

Patients receive trametinib PO 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Whole-Brain Radiotherapy

2012

Completed Phase 2

~150

Therapeutic Conventional Surgery

2005

Completed Phase 3

~9890