Trametinib with/without Radiation for Brain Metastasis

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Antivirals, Antibiotics, Antifungals, Antidepressants

Disqualifiers: Leptomeningeal metastases, Radiosensitive tumors, Lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for patients with cancer that has spread to the brain. The researchers aim to determine the optimal dose and understand the side effects of trametinib (also known as Mekinist), used alone or with whole-brain radiation. Trametinib may stop tumor growth by blocking certain enzymes and might enhance the effectiveness of radiation. People with confirmed brain metastases who can undergo MRI or CT scans are suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you must stop all current medications, but you cannot use other anti-cancer therapies or certain herbal supplements during the study. Some medications that affect trametinib levels should be used with caution, so discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using trametinib with whole brain radiation therapy can be challenging due to its potential harm. Even at doses lower than 1.5 mg, it can cause significant side effects.

However, trametinib alone has been found to be somewhat safe and effective for patients with brain metastases. Some studies with similar drugs have shown that combining trametinib with other treatments is safe for patients with certain types of cancer.

This trial is in its early stages, aiming to determine the safety of trametinib and identify the best dose. This phase is crucial for identifying any safety issues before proceeding to larger studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment options for brain metastasis, which typically include surgery, radiation therapy, and chemotherapy, trametinib offers a unique approach by targeting specific molecular pathways associated with cancer cell growth. Researchers are excited about trametinib because it inhibits a protein known as MEK, which plays a key role in the growth and survival of cancer cells. In the trial, trametinib is being tested in combination with either whole-brain radiation therapy or surgery, offering a potential new avenue for enhancing the effectiveness of existing treatments. This targeted action could lead to more personalized and effective treatment strategies for patients with brain metastases.

What evidence suggests that this trial's treatments could be effective for brain metastases?

This trial will evaluate trametinib in two different treatment arms. In Cohort A, participants will receive trametinib combined with whole-brain radiation therapy (WBRT). Studies have shown mixed results with this combination; one study reported a 33% overall response rate but also highlighted potential side effects. In Cohort B, participants will receive trametinib followed by surgical resection of the tumor. Previous research found that 58% of patients with brain metastases from melanoma responded positively when trametinib was combined with dabrafenib, suggesting trametinib might also be effective on its own against brain tumors. This trial aims to further understand the effectiveness and safety of trametinib in these different treatment settings. ^{2 3 6 7 8}

Who Is on the Research Team?

Joshua D. Palmer, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

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

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

My blood clotting tests are normal or I'm on warfarin.

Exclusion Criteria

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

I cannot stay still for brain radiation treatment.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive trametinib orally once daily. In Cohort A, 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. In Cohort B, patients receive trametinib for 14 days followed by surgical resection of the tumor.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 2 months for 1 year, every 3 months for 3 years, and then every 6 months thereafter.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Trametinib
• Whole-Brain Radiotherapy

Trial Overview 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.

How Is the Trial Designed?

Group I: Cohort B (trametinib, surgery) Experimental Treatment 4 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 Treatment 4 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.

Trametinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Mekinist for:

• Melanoma
• Non-small cell lung cancer

Approved in United States as Mekinist for:

• Melanoma
• Non-small cell lung cancer
• Thyroid cancer

Approved in Canada as Mekinist for:

• Melanoma
• Non-small cell lung cancer

Approved in Japan as Mekinist for:

• Melanoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12133646/

The safety and efficacy of dabrafenib plus trametinib for ... In a phase 2 study, dabrafenib was beneficial in 39.2% of patients with metastatic brain melanoma who had never received medication before, as ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10702308/

Outcomes in patients with BRAFV600–mutated melanoma ... Analysis of pooled survival data from these two studies showed progression-free survival (PFS) rates of 19% at five years, with a five-year OS rate of 34%.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814022001542

Phase I study of trametinib in combination with whole brain ... Even subtherapeutic trametinib doses are toxic with whole brain radiation therapy. •. The overall response rate was 33% with a median survival of 2.2 months.

4. onclive.com onclive.com/view/longterm-and-brain-mets-data-demonstrate-strong-dabrafenibtrametinib-efficacy-in-melanoma

Long-Term and Brain Mets Data Demonstrate Strong ... An analysis of the phase II COMBI-MB trial results showed that dabrafenib plus trametinib achieved an intracranial response (IR) rate of 58% in ...

5. jitc.bmj.com jitc.bmj.com/content/11/4/e005828

Brain metastasis and survival outcomes after first-line ... In our cohort, first-line therapy with BRAF+MEK targeted therapy led to faster development of brain metastases than PD-1±CTLA-4 immune ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40461758/

The safety and efficacy of dabrafenib plus trametinib for ... This study aims to investigate the dabrafenib plus trametinib for patients diagnosed with melanoma brain metastasis (MBM).

7. ejcancer.com ejcancer.com/article/S0959-8049(22)00484-1/fulltext

A subgroup analysis of patients with brain metastases An earlier analysis provided efficacy and safety results of dabrafenib and trametinib in the overall population. Here we report an ...

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.704890/full

Impact of Previous Local Treatment for Brain Metastases ... Conclusions. Vemurafenib, dabrafenib, and dabrafenib plus trametinib demonstrate intracranial activity and safety in BRAF-mutated melanoma ( ...