Trametinib for Hormone-Resistant Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: Abiraterone, Enzalutamide

Must not be taking: Corticosteroids, MAPK inhibitors

Disqualifiers: Cardiovascular disease, Lung disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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: 2

Duration: Up to 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of trametinib for individuals with prostate cancer that no longer responds to hormone treatments and has metastasized. Trametinib may inhibit cancer cell growth by blocking certain enzymes. The trial targets those whose prostate cancer has worsened despite treatments like abiraterone acetate or enzalutamide. Participants should have metastatic prostate cancer that is worsening and have tried at least one other treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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

The trial requires that you stop using any medications or herbal products that may have hormonal anti-prostate cancer activity or affect PSA levels, as well as systemic corticosteroids above a certain dose, within 4 weeks of enrollment. If you're on such medications, you may need to stop them before joining the trial.

Is there any evidence suggesting that trametinib is likely to be safe for humans?

Research has shown that trametinib is under investigation for its potential to help patients with hormone-resistant prostate cancer. This cancer type does not respond to standard hormone treatments and can spread to other parts of the body.

Regarding safety, previous patients have generally tolerated trametinib well. Some studies reported side effects like skin rash, diarrhea, and tiredness, but these are often manageable with medical help. The FDA has already approved trametinib for treating certain types of skin cancer, indicating it has passed important safety checks for that condition.

This trial is in phase 2, meaning researchers are still gathering information on trametinib's safety for prostate cancer patients. However, reaching this stage indicates some evidence of its safety from earlier studies. Trial participants should discuss potential risks and benefits with their healthcare team. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Trametinib is unique because it targets a different pathway in treating hormone-resistant prostate cancer. While most treatments for this condition focus on blocking testosterone or other hormones that fuel cancer growth, trametinib works by inhibiting a protein known as MEK, which is part of a signaling pathway that can promote cancer cell growth and survival. Researchers are excited about trametinib because it offers a novel approach and could potentially be effective for patients who no longer respond to standard hormonal therapies like androgen deprivation therapy. This could open up new avenues for treating a challenging stage of prostate cancer.

What evidence suggests that trametinib might be an effective treatment for hormone-resistant prostate cancer?

Research has shown that trametinib, which participants in this trial will receive, might help treat prostate cancer unresponsive to hormone therapy. This drug blocks certain proteins that cancer cells need to grow. Early findings suggest that trametinib can slow or stop the growth of these cancer cells. It showed promise in patients whose cancer had spread and had not responded to standard hormone treatments. While more research is needed, these early results offer hope for those with advanced prostate cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Matthew Rettig

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Left ventricular ejection fraction (LVEF) >= 45% as measured by echocardiogram during screening evaluation

Aspartate aminotransferase (AST) within the reference range during screening evaluation

My metastatic tumor has been biopsied.

Exclusion Criteria

I have not had any cancer other than non-melanoma skin cancer in the last 5 years.

Patients with intra-cardiac defibrillators or permanent pacemakers

I have had interstitial lung disease or pneumonitis.

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. Treatment continues in the absence of disease progression or unacceptable toxicity.

Up to 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Follow-up at 2 and 4 weeks, then every 4 weeks thereafter

What Are the Treatments Tested in This Trial?

Interventions

• Trametinib

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment (trametinib) Experimental Treatment 3 Interventions

Patients receive trametinib PO QD. Treatment continues 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?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02881242?intr=JTP-74057&aggFilters=studyType:int&viewType=Table&rank=9

Trametinib in Treating Patients With Progressive Metastatic ... This phase II trial studies how well trametinib works in treating patients with hormone-resistant prostate cancer that is growing or getting worse and has ...

2. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT02881242

UCLA Prostate Cancer Trial → Trametinib in Treating Patients ... This phase II trial studies how well trametinib works in treating patients with hormone-resistant prostate cancer that is growing or getting ...

3. withpower.com withpower.com/trial/phase-3-carcinoma-2018-29059

Trametinib for Hormone-Resistant Prostate Cancer This trial studies how well trametinib works in patients with advanced prostate cancer that has not responded to typical hormone treatments.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03386071

Progressive Metastatic Castrate Resistant Prostate Cancer ... Trametinib may also be stopped completely at his Treating Physician's discretion. The treating physician will use his/her clinical expertise considering the ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2016-01201

Trametinib in Treating Patients with Progressive Metastatic ... This phase II trial studies how well trametinib works in treating patients with castration-resistant prostate cancer that is growing or getting worse.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02881242

Trametinib in Treating Patients With Progressive Metastatic ... This phase II trial studies how well trametinib works in treating patients with hormone-resistant prostate cancer that is growing or getting worse and has ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2015-01448

Effects of Endocrine Therapy with or without Trametinib ... This phase II trial studies the effects of endocrine (hormone) therapy when given with or without treatment that targets cancer cells (trametinib or ...

8. clinicaltrials.ucbraid.org clinicaltrials.ucbraid.org/trial/NCT02881242

Trametinib in Treating Patients With Progressive Metastatic ... This phase II trial studies how well trametinib works in treating patients with hormone-resistant prostate cancer that is growing or getting worse and has ...