Trametinib + Paclitaxel for Thyroid Cancer

Not currently recruiting at 9 trial locations

Overseen By David G. Pfister, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Herbal supplements

Disqualifiers: Brain metastases, Cardiovascular risk, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for anaplastic thyroid cancer, a rare and aggressive form of thyroid cancer. The researchers aim to determine if paclitaxel (a chemotherapy medication) and trametinib (a targeted therapy) can be safely used together and how they affect the cancer's growth or shrinkage. Individuals diagnosed with anaplastic thyroid cancer that cannot be surgically removed and who have noticeable disease growth might be suitable for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does prohibit the use of certain herbal supplements and any medications that are not allowed during the study. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this treatment combination is likely to be safe for humans?

Research has shown that combining trametinib with paclitaxel may help treat anaplastic thyroid cancer. A small initial study found that most patients tolerated this combination well. Some experienced side effects, but these were usually mild. Common issues included tiredness and low blood cell counts, typical with cancer treatments.

Paclitaxel is already a common treatment for this cancer, so its safety is well-known. Trametinib is also approved for other cancers, indicating it is generally safe. This treatment remains in early testing, so more information is needed to confirm these results. However, early findings are promising for safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for thyroid cancer?

Unlike the standard treatments for thyroid cancer, which often include surgery, radioactive iodine, and external beam radiation, the combination of Trametinib and Paclitaxel offers a unique approach. Trametinib is a targeted therapy that blocks a specific protein in cancer cells called MEK, which is involved in their growth and survival. This mechanism is different from traditional therapies that might not target specific cancer pathways. Researchers are excited about this combination because it could potentially improve outcomes for patients with anaplastic thyroid cancer, a particularly aggressive form of the disease, by directly interfering with cancer cell proliferation.

What evidence suggests that this treatment might be an effective treatment for thyroid cancer?

Research has shown that combining trametinib with paclitaxel may effectively treat anaplastic thyroid cancer. In one study, 25% of patients did not experience cancer progression for at least 6 months, with an average survival time of about 26 weeks. This indicates that some patients lived longer without their cancer worsening. In this trial, participants will receive trametinib combined with paclitaxel. Trametinib reduces the size of thyroid tumors and enhances the effectiveness of treatments like paclitaxel. Although anaplastic thyroid cancer is very aggressive, this combination offers hope for better outcomes compared to standard treatments. ^{1 3 4 6 7}

Who Is on the Research Team?

Eric Sherman, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with anaplastic thyroid cancer that can't be removed by surgery. Participants must be able to take pills, agree to use birth control, and have a certain level of physical ability (ECOG ≤2 or Karnofsky ≥60). They should not have significant nerve damage, gastrointestinal issues, recent chemotherapy or radiotherapy, untreated brain metastases, lung disease history, high cardiovascular risk, active infections like HIV/HBV/HCV or conditions affecting oral medication absorption.

Inclusion Criteria

Agreement to use adequate contraception

Ability to understand and sign a written informed consent document

Women who can have babies must have a negative pregnancy test within 14 days before joining the study.

Exclusion Criteria

I have been diagnosed with HIV, HBV, or HCV.

I do not have any unmanaged ongoing illnesses.

I have a condition that affects my ability to absorb pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive paclitaxel 80mg/m^2 weekly for 3 out of 4 weeks in combination with trametinib 2mg daily during each 4 week cycle

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel
• Trametinib

Trial Overview

The study tests the combination of Trametinib and Paclitaxel on anaplastic thyroid cancer. It aims to assess safety and how well this combo works in slowing down tumor growth or causing shrinkage. The effects will be measured according to standard criteria for evaluating the response of solid tumors.

How Is the Trial Designed?

Group I: Trametinib in Combination With Paclitaxel Experimental Treatment 2 Interventions

Patients will receive paclitaxel 80mg/m\^2 weekly for 3 out of 4 weeks, which is a standard regimen in the treatment of anaplastic thyroid cancer, in combination with trametinib 2mg daily during each 4 week cycle.

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

Approved in United States as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in European Union as Taxol for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Approved in Canada as Paclitaxel for:

• Ovarian cancer
• Breast cancer
• Non-small cell lung cancer
• Kaposi's sarcoma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

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

Published Research Related to This Trial

In a study of 30 women with advanced breast cancer, the combination of doxorubicin and paclitaxel resulted in a high overall response rate of 83%, with 24% achieving complete remission, indicating strong efficacy for this treatment regimen.

However, the treatment was associated with significant toxicities, including neutropenia and cardiotoxicity, with 50% of patients experiencing reduced heart function and 20% developing congestive heart failure, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Gehl, J., Boesgaard, M., Paaske, T., et al.[2020]

In a phase II trial involving 16 patients with BRAF V600E-mutated anaplastic thyroid cancer, the combination of dabrafenib and trametinib showed a high overall response rate of 69%, indicating significant efficacy in a cancer type with previously limited treatment options.

The treatment was well tolerated, with common side effects including fatigue, fever, and nausea, and no new safety concerns were identified, marking a promising advancement for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. Subbiah, V., Kreitman, RJ., Wainberg, ZA., et al.[2022]

Capivasertib, an oral AKT inhibitor, was well tolerated when combined with weekly paclitaxel in patients with advanced ER+/HER2- breast cancer, with a recommended dosing schedule of 400 mg twice daily for 4 days on and 3 days off.

However, the addition of capivasertib did not significantly improve progression-free survival compared to placebo, with median PFS of 10.9 months for capivasertib versus 8.4 months for placebo in the overall population, indicating it may not enhance treatment outcomes in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Turner, NC., Alarcón, E., Armstrong, AC., et al.[2023]

Docetaxel is an effective chemotherapy drug that works by binding to microtubules, leading to cell-cycle arrest and apoptosis, and is approved for various cancers including breast, lung, prostate, and recently advanced gastric cancer.

While docetaxel can cause severe neutropenia as a major side effect, alternative dosing schedules have been developed to reduce this toxicity, making it safer for patients with compromised bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. Ramaswamy, B., Puhalla, S.[2018]

Docetaxel is an effective treatment for advanced non-small cell lung cancer (NSCLC), showing survival benefits in both first- and second-line therapy, and is comparable or superior to other platinum-based chemotherapy options.

The drug has a manageable toxicity profile and has shown promising results when combined with novel targeted agents in Phase II studies, indicating its versatility in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. Wakelee, H., Ramalingam, S., Belani, CP.[2018]

In a study of 36 patients with BRAF V600E-mutant anaplastic thyroid cancer, the combination of dabrafenib and trametinib showed a significant overall response rate of 56%, with three patients achieving complete responses.

The treatment demonstrated manageable safety, with no new adverse effects identified, and improved median progression-free survival of 6.7 months and overall survival of 14.5 months, indicating it is a promising option for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study. Subbiah, V., Kreitman, RJ., Wainberg, ZA., et al.[2022]

In a study of 27 patients with anaplastic thyroid carcinoma (ATC), those treated with the combination of Dabrafenib and Trametinib (DT) had a median overall survival of 475 days, significantly longer than the 156 days for multimodal therapy and 39 days for compassionate care (P < .001).

The DT group also demonstrated a median progression-free survival of 270 days, compared to less than 32 days for BRAF wild type patients, with no severe adverse events reported, indicating a strong safety and efficacy profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target therapy for BRAF mutated anaplastic thyroid cancer: a clinical and molecular study. da Silva, TN., Rodrigues, R., Saramago, A., et al.[2023]

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