Trametinib + Paclitaxel for Thyroid Cancer

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

13 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Trametinib and Paclitaxel for thyroid cancer?

Research shows that Trametinib, when used with other drugs, can effectively shrink thyroid tumors and enhance the effectiveness of other treatments. Paclitaxel has been shown to increase the effectiveness of certain cancer treatments, suggesting that combining it with Trametinib could be beneficial for thyroid cancer. ^{1 2 3 4 5}

Is the combination of Trametinib and Paclitaxel safe for humans?

Trametinib has been studied in combination with other drugs like dabrafenib for thyroid cancer, showing it is generally well tolerated with common side effects like fatigue and nausea. Paclitaxel, used in various cancers, can cause side effects such as fatigue and nausea, but these are usually manageable. No new safety concerns were identified in these studies. ^{4 6 7 8 9}

What makes the drug combination of Trametinib and Paclitaxel unique for thyroid cancer?

The combination of Trametinib and Paclitaxel is unique for thyroid cancer because Trametinib targets specific proteins involved in cancer cell growth, while Paclitaxel disrupts cell division, offering a novel approach compared to standard treatments that may not specifically target these pathways. ^{10 11 12 13 14}

What is the purpose of this trial?

The purpose of this study is to test the safety and tolerability of this treatment combination of paclitaxel and trametinib. Additionally, this study aims to to find out what effects the combination of paclitaxel and trametinib has on the shrinkage and growth of anaplastic thyroid cancer.

Research Team

Eric Sherman, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

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

Agreement to use adequate contraception

Ability to understand and sign a written informed consent document

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Target therapy for BRAF mutated anaplastic thyroid cancer: a clinical and molecular study. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

BCL2L11 Induction Mediates Sensitivity to Src and MEK1/2 Inhibition in Thyroid Cancer. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: Visibly curative effect of dabrafenib and trametinib on advanced thyroid carcinoma in 2 patients. [2023]

4. Greece pubmed.ncbi.nlm.nih.gov

Trametinib with and without pazopanib has potent preclinical activity in thyroid cancer. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Modulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by chemotherapy in thyroid cancer cell lines. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. [2022]

7. England 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. [2022]

8. Ukraine pubmed.ncbi.nlm.nih.gov

INHIBITOR OF THE TRANSCRIPTION FACTOR NF-κB, DHMEQ, ENHANCES THE EFFECT OF PACLITAXEL ON CELLS OF ANAPLASTIC THYROID CARCINOMA IN VITRO AND IN VIVO. [2019]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Targeted Therapy for Anaplastic Thyroid Carcinoma: Advances and Management. [2023]

10. Spain pubmed.ncbi.nlm.nih.gov

Docetaxel: a tubulin-stabilizing agent approved for the management of several solid tumors. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. [2020]

12. England 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. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin as first-line chemotherapy combined with gefitinib (IRESSA) in patients with advanced breast cancer: a phase I/II study conducted by the Hellenic Cooperative Oncology Group. [2018]

14. England pubmed.ncbi.nlm.nih.gov

Docetaxel in advanced non-small cell lung cancer. [2018]