Trametinib for Ovarian Cancer

No longer recruiting at 596 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Herbal supplements

Disqualifiers: Brain metastases, Bowel obstruction, Cardiovascular risk, 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: Unknown

Duration: 28 days per cycle, up to progression

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called trametinib (also known as Mekinist) to determine if it outperforms standard treatments for patients with low-grade ovarian cancer that has recurred, worsened, or spread. Trametinib may inhibit cancer cell growth by blocking certain necessary enzymes. The trial compares trametinib to other treatments like letrozole and tamoxifen. It suits patients whose ovarian cancer has returned after at least one round of chemotherapy. As a Phase 2 trial, this research measures trametinib's effectiveness in an initial, smaller group, offering a chance to benefit from a potentially effective treatment.

Will I have to stop taking my current medications?

The trial requires that any hormonal therapy directed at the tumor be stopped at least one week before joining, and any other cancer treatments, including chemotherapy and radiation, must be stopped at least four weeks before joining. Herbal supplements are also not allowed during the study.

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

Research has shown that trametinib is generally well-tolerated by patients. Common side effects include skin rash, diarrhea, and high blood pressure, which are usually manageable and not severe. Studies have demonstrated that trametinib can help patients live longer without their cancer worsening compared to other treatments, making it a promising option for some ovarian cancer patients.

Trametinib is currently being tested in the later stages of clinical trials, indicating sufficient evidence to support its safety for more patients. However, individual experiences can vary. It is essential to discuss potential risks and benefits with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for ovarian cancer, which often include hormone therapies like letrozole and tamoxifen or chemotherapies such as paclitaxel and doxorubicin, trametinib offers a fresh approach by specifically targeting the MEK pathway—a crucial part of the cell growth process in cancer cells. Researchers are excited about trametinib because it has a unique mechanism of action that may effectively inhibit tumor growth at a molecular level, potentially offering better control over cancer progression. This targeted approach could lead to improved outcomes for patients who have not responded well to existing treatments.

What evidence suggests that trametinib might be an effective treatment for ovarian cancer?

Research has shown that trametinib, an oral medication, can effectively treat low-grade serous ovarian cancer. In this trial, some participants will receive trametinib. Studies have found that it allows people to live for about 13 months on average without their cancer worsening, compared to just over 7 months for those on standard treatments. Another study found that trametinib significantly improved the time patients lived without their cancer progressing and increased the percentage of patients whose cancer shrank or disappeared after treatment. These results suggest that trametinib may be a promising option for patients with recurring or worsening ovarian cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

David M Gershenson

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with recurrent or progressive low-grade ovarian cancer or peritoneal cavity cancer who have previously undergone at least one platinum-based chemotherapy. They must not have received certain inhibitor therapies, be able to swallow oral medication, and meet specific health criteria including organ function tests. Pregnant women, nursing mothers, and those with serious medical risks are excluded.

Inclusion Criteria

I am following the birth control and pregnancy guidelines for Trametinib.

I stopped my cancer hormone therapy at least a week ago.

I stopped any cancer treatments like chemo or radiation 4 weeks ago.

Exclusion Criteria

I have not been treated with MEK, KRAS, or BRAF inhibitors.

I need medication that can affect my heart's rhythm.

I have a history or risk of blocked blood vessels in my eye.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive either trametinib or a clinician's choice of standard therapy. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle, up to progression

Multiple visits per cycle for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

2 years every 3 months, 3 years every 6 months, then annually for 5 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Trametinib

Trial Overview

The effectiveness of trametinib is being compared to standard treatments (letrozole, tamoxifen, paclitaxel, pegylated liposomal doxorubicin hydrochloride or topotecan) in this phase II/III trial. Trametinib aims to inhibit enzymes needed for tumor cell growth and its performance will be measured against existing therapies.

How Is the Trial Designed?

Group I: Arm B (trametinib) Experimental Treatment 2 Interventions

Patients receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: Arm A (letrozole, tamoxifen, paclitaxel, PLD, topotecan) Active Control 7 Interventions

Patients receive clinician's choice of either letrozole PO QD on days 1-28, tamoxifen citrate PO BID on days 1-28, paclitaxel IV over 1 hour on days 1, 8, and 15, pegylated liposomal doxorubicin hydrochloride IV over 1 hour on day 1, or topotecan IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients developing progressive disease may cross over to Arm B.

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+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

The pediatric oral solution of trametinib showed improved bioavailability compared to the tablet formulation, with significant increases in key pharmacokinetic measures such as Cmax and AUC, indicating it may be more effective in delivering the drug to patients.

The safety profile of the trametinib pediatric oral solution was consistent with existing data, with no serious adverse events leading to withdrawal from the study, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative bioavailability of pediatric oral solution and tablet formulations of trametinib in adult patients with solid tumors. Cox, DS., Allred, A., Zhou, Y., et al.[2018]

In a phase 3 trial involving 36 patients with untreated BRAF V600-mutant metastatic melanoma, the combination of spartalizumab, dabrafenib, and trametinib resulted in a high objective response rate of 78%, with 44% achieving complete responses.

While the treatment showed promising efficacy, 72% of patients experienced severe treatment-related adverse events, and 17% had to permanently discontinue the therapy due to these side effects, highlighting the need for careful monitoring and management of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined PD-1, BRAF and MEK inhibition in advanced BRAF-mutant melanoma: safety run-in and biomarker cohorts of COMBI-i. Dummer, R., Lebbé, C., Atkinson, V., et al.[2022]

Citations

1.

thelancet.com

thelancet.com/journals/lancet/article/PIIS0140-6736(21)02175-9/fulltext

Trametinib versus standard of care in patients with ...

Our study shows that the use of the oral MEK inhibitor trametinib significantly increased progression-free survival and objective response rate ...

2.

cancer.gov

cancer.gov/news-events/cancer-currents-blog/2022/trametinib-low-grade-serous-ovarian-cancer

Trametinib to Treat Low-Grade Serous Ovarian Cancer - NCI

People in the trametinib group survived for a median of 13 months without dying or having their cancer progress, compared with just over 7 ...

3.

annalsofoncology.org

annalsofoncology.org/article/S0923-7534(21)03414-1/fulltext

743P Real-world outcomes in patients treated with ...

Median duration of treatment was 5.0m. Best response was partial response (PR) in 21%, stable disease (SD) in 32%, progressive disease (PD) in 36% and ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7042411/

Trametinib response in heavily pretreated high-grade ...

The study demonstrated that trametinib significantly improved clinical outcomes in women with recurrent LGSOC. 2. Case report. The timeline of ...

5.

england.nhs.uk

england.nhs.uk/wp-content/uploads/2023/11/2253-trametinib-evidence-review.pdf

Evidence review: Trametinib in recurrent or progressive ...

This evidence review examines the clinical effectiveness, safety, and cost effectiveness of trametinib compared with standard of care in people with ...

6.

onclive.com

onclive.com/view/trametinib-represents-a-new-standard-of-care-option-in-recurrent-low-grade-serous-ovarian-carcinoma

Trametinib Represents a New Standard-of-Care Option in ...

The MEK inhibitor trametinib reduced the risk of disease progression or death by 52% compared with current standard-of-care therapies in ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6374783/

Response to trametinib in recurrent low-grade serous ovarian ...

Trametinib was effective in low grade ovarian cancer with NRAS mutation. · Next generation sequencing of tumors can provide new options. · Common side effects of ...