What side effects are associated with this type of intervention?

Common treatments for prostate cancer, including MEK inhibitors like trametinib, can have various side effects. Trametinib may cause diarrhea, rash, fatigue, and nausea. Lutetium Lu 177 vipivotide tetraxetan is associated with myelosuppression, nephrotoxicity, and salivary gland toxicity. Cabazitaxel can lead to neutropenia, diarrhea, and fatigue. Androgen receptor-directed therapies often result in hot flashes, fatigue, and cardiovascular issues. These side effects should be discussed with a healthcare provider to tailor the treatment plan to the patient's needs and tolerances.

What prior FDA approvals exist?

FDA-approved treatments for prostate cancer include a variety of therapies targeting different pathways. While trametinib, a MEK inhibitor, is being studied for hormone-resistant prostate cancer, other approved treatments include androgen receptor pathway inhibitors like enzalutamide and abiraterone, as well as chemotherapeutic agents such as docetaxel and cabazitaxel. Additionally, radioligand therapy with lutetium Lu 177 vipivotide tetraxetan has shown efficacy in PSMA-positive metastatic castration-resistant prostate cancer. Immunotherapies like sipuleucel-T and checkpoint inhibitors are also part of the treatment landscape.

What other types of research exist?

Promising novel alternatives to Trametinib for prostate cancer patients include new antiandrogen compounds and investigational agents targeting specific pathways such as the PI3K/PTEN/AKT/mTOR pathway. Examples include temsirolimus and everolimus, which have shown some efficacy in clinical trials. Additionally, selective RET inhibitors like selpercatinib and pralsetinib, although primarily used for thyroid cancers, are being explored for their potential in other cancers.

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Kinase Inhibitor

Trametinib for Hormone-Resistant Prostate Cancer

Phase 2

Waitlist Available

Led By Matthew Rettig

Research Sponsored by Jonsson Comprehensive Cancer Center

Eligibility Criteria Checklist

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

Must have

Metastatic tumor that has been biopsied

Histologically confirmed prostate cancer (not exclusive of adenocarcinoma)

Must not have

History of interstitial lung disease or pneumonitis

Use of any medication or herbal products that may have hormonal anti-prostate cancer activity and/or are known to modulate PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of enrollment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 24 weeks

Awards & highlights

Summary

This trial studies how well trametinib works in patients with advanced prostate cancer that has not responded to typical hormone treatments. Trametinib aims to stop cancer cells from growing by blocking essential enzymes.

Who is the study for?

This trial is for men with advanced prostate cancer that has spread and no longer responds to hormone therapy. Participants must have low testosterone levels maintained by ongoing therapy, adequate heart function, good blood counts, normal liver and kidney function, and be able to consent. They should not have other serious health issues or a history of certain heart diseases.

What is being tested?

The study is testing Trametinib's effectiveness in stopping tumor growth by inhibiting specific enzymes needed for cell growth in patients with metastatic hormone-resistant prostate cancer. It includes laboratory biomarker analysis and quality-of-life assessments.

What are the potential side effects?

Trametinib may cause side effects such as skin rash, diarrhea, fatigue, nausea, swelling in the face or limbs (peripheral edema), high blood pressure (hypertension), shortness of breath (dyspnea), abnormal bleeding or bruising due to low platelet count (thrombocytopenia), vision changes like blurred vision or reduced visual acuity.

Eligibility Criteria

Inclusion Criteria

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

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My metastatic tumor has been biopsied.

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My prostate cancer diagnosis was confirmed through a tissue examination.

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My blood clotting time is within the safe range.

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I am on therapy to keep my testosterone levels below 50 ng/dL.

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I am able to care for myself and perform daily activities.

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My prostate cancer has worsened despite treatment with abiraterone and/or enzalutamide.

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I am willing to have a biopsy if my cancer gets worse.

Exclusion Criteria

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

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I have had interstitial lung disease or pneumonitis.

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I haven't taken any prostate cancer or PSA affecting meds, or high-dose steroids recently.

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I have brain metastasis or spinal issues related to my cancer.

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I have a stomach or bowel condition that affects how my body absorbs food.

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My heart's pumping ability is below 45%.

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I have had a heart attack, unstable angina, or a procedure to open my heart's arteries within the last 6 months.

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I am not taking medications that affect hormone levels.

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I have had or am at risk for a specific eye condition (RPED).

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I have severe heart failure.

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I do not have any health conditions that would stop me from following the study's requirements.

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I have previously used trametinib or a similar drug.

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I have a history of serious heart rhythm problems.

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I have had retinal vein occlusion or am at risk for it.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 24 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 24 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 24 weeks for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Response rate assessed by RECIST criteria

Secondary study objectives

Change in markers of cell proliferation (Ki67) and apoptosis (p27), assessed by immunohistochemistry

Change in trametinib target engagement of MEK1/2 defined by the presence of p-ERK, assessed by immunohistochemistry

Molecular correlates defined by gene expression, assessed using ribonucleic acid-sequencing, and mutational events, assessed using DNA exome-seq

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (trametinib)Experimental Treatment3 Interventions

Patients receive trametinib PO QD. Treatment continues in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trametinib

2014

Completed Phase 2

~1550

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments primarily include androgen deprivation therapy (ADT), immune checkpoint inhibitors, and targeted therapies such as MEK inhibitors. ADT works by reducing androgen levels or blocking androgen receptors, which are crucial for prostate cancer cell growth. Immune checkpoint inhibitors, like pembrolizumab, enhance the immune system's ability to recognize and attack cancer cells. MEK inhibitors, such as trametinib, block the MEK enzyme in the MAPK/ERK pathway, which is involved in cell division and survival. These treatments are significant for prostate cancer patients as they target specific mechanisms that drive cancer progression, offering more personalized and potentially effective treatment options.

A Phase I Trial of the VEGF Receptor Tyrosine Kinase Inhibitor Pazopanib in Combination with the MEK Inhibitor Trametinib in Advanced Solid Tumors and Differentiated Thyroid Cancers.Prodding the Beast: Assessing the Impact of Treatment-Induced Metastasis.Intervention in the context of development: pathways toward new treatments.