Triple Drug Therapy for Thyroid Cancer

Recruiting at 9 trial locations

Overseen By Davic Pfister, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Dabrafenib, Trametinib

Must not be taking: Antiretrovirals, Idelalisib

Disqualifiers: Brain metastases, Lung disease, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

16 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are HIV-positive and on antiretroviral therapy, you are not eligible to participate.

What data supports the effectiveness of the drug combination used in the Triple Drug Therapy for Thyroid Cancer?

The combination of dabrafenib and trametinib has been approved for treating BRAF V600E-mutant anaplastic thyroid cancer, showing effectiveness in clinical studies. This suggests that the combination of these drugs can be beneficial for certain types of thyroid cancer. ^{1 2 3 4 5}

Is the triple drug therapy for thyroid cancer safe?

The combination of dabrafenib and trametinib has been generally well tolerated in patients with thyroid cancer, with common side effects including fatigue, fever, and nausea. However, there have been rare cases of serious neurological side effects like Guillain-Barre syndrome, which is important for patients and doctors to be aware of. ^{4 6 7 8 9}

What makes the triple drug therapy for thyroid cancer unique?

The triple drug therapy for thyroid cancer is unique because it combines Cemiplimab, Dabrafenib, and Trametinib, which target different pathways involved in cancer growth. Cemiplimab is an immunotherapy that helps the immune system attack cancer cells, while Dabrafenib and Trametinib target specific proteins involved in cell growth, making this combination potentially more effective than using each drug alone. ^{10 11 12 13 14}

What is the purpose of this trial?

This study is being done to see if adding the study drug, cemiplimab, to the standard therapy with dabrafenib and trametinib is an effective treatment against 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 has a specific BRAF-V600E mutation. It's open to those who haven't been cured by surgery, can undergo biopsies, and have measurable disease. Participants need normal heart function and organ health, must not be pregnant, agree to use contraception, and be able to take oral meds.

Inclusion Criteria

My organ and bone marrow functions are normal.

I can swallow and keep down pills.

Negative pregnancy test within 14 days of registration for women of childbearing potential

Exclusion Criteria

I have been treated with dabrafenib and trametinib.

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

I have interstitial lung disease or pneumonitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cemiplimab in combination with dabrafenib and trametinib

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cemiplimab
• Dabrafenib
• Trametinib

Trial Overview The study tests if adding cemiplimab (a new drug) to standard treatment with dabrafenib and trametinib improves outcomes in anaplastic thyroid cancer. Patients will receive this combination therapy and their response will be monitored.

Participant Groups

Group I: BRAF-mutant ATC Experimental Treatment 2 Interventions

Participants will have a diagnosis of BRAF-V600E mutant Anaplastic Thyroid Cancer

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

Approved in European Union as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in United States as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Basal cell carcinoma (BCC)
• Non-small cell lung cancer (NSCLC)

Approved in Canada as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)
• Non-small cell lung cancer (NSCLC)

Approved in Brazil as Libtayo for:

• Cutaneous squamous cell carcinoma (CSCC)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

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 phase 2 trial involving 53 patients with BRAF-mutated radioactive iodine refractory differentiated thyroid cancer, both dabrafenib monotherapy and the combination of dabrafenib + trametinib showed similar objective response rates, with 42% and 48% respectively, indicating no significant advantage of the combination therapy.

The most common side effects included skin disorders and fever, but there were no treatment-related deaths, suggesting that both treatment options are relatively safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dabrafenib Versus Dabrafenib + Trametinib in BRAF-Mutated Radioactive Iodine Refractory Differentiated Thyroid Cancer: Results of a Randomized, Phase 2, Open-Label Multicenter Trial. Busaidy, NL., Konda, B., Wei, L., 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]

Birinapant, a drug that targets inhibitors of apoptosis proteins (IAPs), shows promise as a treatment for triple-negative breast cancer (TNBC) by enhancing the effectiveness of gemcitabine, a commonly used chemotherapy drug.

In both laboratory and mouse models, birinapant was found to activate the intrinsic apoptosis pathway, leading to increased cancer cell death when used alongside gemcitabine, suggesting a new therapeutic strategy for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Birinapant Enhances Gemcitabine's Antitumor Efficacy in Triple-Negative Breast Cancer by Inducing Intrinsic Pathway-Dependent Apoptosis. Xie, X., Lee, J., Liu, H., et al.[2022]

In a study investigating treatments for HER2+ breast cancer and triple-negative breast cancer (TNBC), combining neratinib with everolimus (an mTOR inhibitor) or trametinib (a MEK inhibitor) significantly enhanced tumor growth inhibition compared to using neratinib alone, achieving up to 81% inhibition in xenograft models.

The combination therapies not only improved anti-tumor effects but also activated apoptosis pathways, indicating a potential mechanism for their enhanced efficacy, making these combinations promising options for treating these aggressive breast cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PI3K and MAPK Pathways as Targets for Combination with the Pan-HER Irreversible Inhibitor Neratinib in HER2-Positive Breast Cancer and TNBC by Kinome RNAi Screening. Lee, J., Liu, H., Pearson, T., et al.[2021]

In a study of 247 patients with metastatic hormone receptor-positive, PIK3CA-mutant breast cancer, 61.5% developed any-grade hyperglycemia after treatment with alpelisib, with a median onset time of just 16 days.

Patients receiving alpelisib as standard care experienced significantly higher rates of hyperglycemia compared to those in clinical trials, highlighting the importance of monitoring and optimizing glycemic status before starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. Shen, S., Chen, Y., Carpio, A., et al.[2023]

References

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

Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond. [2023]

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

The Akt inhibitor MK2206 synergizes, but perifosine antagonizes, the BRAF(V600E) inhibitor PLX4032 and the MEK1/2 inhibitor AZD6244 in the inhibition of thyroid cancer cells. [2022]

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

Thyroid Cancers: From Surgery to Current and Future Systemic Therapies through Their Molecular Identities. [2023]

4. 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]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Clinical and Translational Challenges in Thyroid Cancer. [2020]

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

Dabrafenib Versus Dabrafenib + Trametinib in BRAF-Mutated Radioactive Iodine Refractory Differentiated Thyroid Cancer: Results of a Randomized, Phase 2, Open-Label Multicenter Trial. [2023]

7. 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]

8. China pubmed.ncbi.nlm.nih.gov

Advances in targeted therapy for anaplastic thyroid carcinoma. [2022]

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

Guillain-Barre Syndrome Secondary to the Use of Dabrafenib and Trametinib for the Treatment of Advanced Thyroid Carcinoma. [2023]

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

Birinapant Enhances Gemcitabine's Antitumor Efficacy in Triple-Negative Breast Cancer by Inducing Intrinsic Pathway-Dependent Apoptosis. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Current landscape of personalized clinical treatments for triple-negative breast cancer. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

PI3K and MAPK Pathways as Targets for Combination with the Pan-HER Irreversible Inhibitor Neratinib in HER2-Positive Breast Cancer and TNBC by Kinome RNAi Screening. [2021]

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

HDAC6 inhibition enhances the anti-tumor effect of eribulin through tubulin acetylation in triple-negative breast cancer cells. [2021]

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

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. [2023]