Sorafenib + Everolimus for Thyroid Cancer

Recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

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: Until disease progression or unacceptable adverse events

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies the effects, good and bad, of using everolimus along with sorafenib tosylate versus sorafenib tosylate alone in treating patients with advanced radioactive iodine refractory thyroid cancer. Sorafenib tosylate and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of everolimus to sorafenib tosylate may cause more shrinkage of thyroid cancer and may prevent it from growing but it could also cause more side effects than sorafenib tosylate alone. It is not yet known whether this treatment with sorafenib tosylate and everolimus is better, the same, or worse than sorafenib tosylate alone.

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

The trial requires that you stop taking any strong inhibitors or inducers of CYP3A4 (a liver enzyme) at least 14 days before starting the study. If you are on anticoagulation medication, you must be on a stable dose before joining the trial. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What evidence supports the effectiveness of the drugs Sorafenib and Everolimus for thyroid cancer?

Sorafenib has shown promise in treating advanced thyroid cancer, with studies indicating it can help control the disease in various thyroid cancer types, including those not responding to traditional treatments. Although Everolimus is not specifically mentioned in the provided studies, Sorafenib's effectiveness in thyroid cancer suggests potential benefits when combined with other similar drugs. ^{1 2 3 4 5}

Is the combination of Sorafenib and Everolimus safe for treating thyroid cancer?

Sorafenib, used for thyroid cancer, often causes side effects like skin reactions, diarrhea, and hair loss, and many patients stop or adjust their dose due to these issues. Everolimus has been studied for safety in thyroid cancer, but specific safety data for the combination of Sorafenib and Everolimus is not provided in the available research. ^{1 6 7 8 9}

How does the drug Sorafenib Tosylate differ from other treatments for thyroid cancer?

Sorafenib Tosylate is unique because it is a multikinase inhibitor that targets specific proteins involved in tumor growth and blood vessel formation, making it effective for advanced thyroid cancer that doesn't respond to traditional treatments like surgery or radioactive iodine. It has shown promise in stabilizing the disease and improving outcomes in patients with aggressive forms of thyroid cancer. ^{1 2 3 4 10}

Research Team

Eric Sherman, M.D.

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with advanced Hurthle cell thyroid cancer that hasn't responded to radioactive iodine treatment can join. They should have measurable disease, no recent major surgery, and their blood counts and liver function need to be within certain limits. No prior sorafenib or mTOR inhibitors for thyroid cancer, no brain metastasis, and a good performance status are required.

Inclusion Criteria

I have never used sorafenib or mTOR inhibitors for thyroid cancer.

I have never had cancer spread to my brain.

My thyroid cancer has been confirmed to be Hürthle cell type.

Exclusion Criteria

I have never had chronic active hepatitis.

I have not had a GI fistula or perforation in the last 90 days.

I do not have a history of prolonged QT syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sorafenib with or without everolimus. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Until disease progression or unacceptable adverse events

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Treatment Details

Interventions

• Everolimus
• Sorafenib Tosylate

Trial Overview The trial is testing if adding everolimus to sorafenib tosylate improves outcomes in patients with this type of thyroid cancer. Participants will either receive both drugs or only sorafenib tosylate, randomly assigned, to see which approach is more effective at stopping tumor growth.

Participant Groups

Group I: sorafenib and everolimus Experimental Treatment 2 Interventions

Patients receive sorafenib 400 mg PO twice daily and everolimus 5 mg PO once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group II: sorafenib Active Control 1 Intervention

Patients receive sorafenib 400 mg PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may cross over and receive everolimus 10 mg PO once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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 phase 2 study involving 36 patients with radioactive iodine-refractory thyroid carcinoma, the combination of sorafenib and temsirolimus resulted in a partial response rate of 22%, indicating improved efficacy compared to sorafenib alone, which had a response rate of only 12.2%.

The combination treatment showed a progression-free survival rate of 30.5% at one year, particularly benefiting patients who had not received prior systemic treatments, suggesting that this regimen could be a promising option for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer. Sherman, EJ., Dunn, LA., Ho, AL., et al.[2018]

References

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

Phase 2 study evaluating the combination of sorafenib and temsirolimus in the treatment of radioactive iodine-refractory thyroid cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Sorafenib in metastatic thyroid cancer. [2018]

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

Phase II trial of sorafenib in advanced thyroid cancer. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Sorafenib and thyroid cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Treatment of advanced thyroid cancer with targeted therapies: ten years of experience. [2022]

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

Toxic Effects of Sorafenib in Patients With Differentiated Thyroid Carcinoma Compared With Other Cancers. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population. [2022]

8. England pubmed.ncbi.nlm.nih.gov

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes. [2022]

9. France pubmed.ncbi.nlm.nih.gov

Sorafenib: a review of its use in patients with radioactive iodine-refractory, metastatic differentiated thyroid carcinoma. [2022]

10. Italy pubmed.ncbi.nlm.nih.gov

Aggressive thyroid cancer: targeted therapy with sorafenib. [2021]