Sorafenib + Everolimus for Thyroid Cancer

Not currently recruiting at 20 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Brain metastasis, Cardiovascular disease, Liver disease, 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: Until disease progression or unacceptable adverse events

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding everolimus, an mTOR inhibitor, to sorafenib, a cancer treatment drug, can more effectively treat advanced thyroid cancer unresponsive to radioactive iodine. Researchers aim to determine if this combination can shrink tumors or prevent their growth better than sorafenib alone, while also monitoring for additional side effects. The trial is open to individuals with thyroid cancer that has spread or cannot be surgically removed, particularly if radioactive iodine treatment was ineffective. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research has shown that sorafenib is generally well-tolerated for treating thyroid cancer. Patients taking sorafenib often experience longer periods without their cancer worsening. Common side effects include tiredness, diarrhea, and skin reactions on the hands and feet, but these are usually manageable.

Studies suggest that adding everolimus to sorafenib might enhance the treatment's effectiveness. This combination can help patients go longer without disease progression, though it may cause more side effects. However, these side effects are not significantly worse than those from sorafenib alone. Common side effects include mouth sores and tiredness.

Overall, both treatments have been used in medical settings and are considered relatively safe, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Sorafenib and Everolimus for thyroid cancer because it offers a dual approach to targeting the disease. While most treatments for thyroid cancer, like radioactive iodine or surgery, focus on removing or irradiating cancer cells, Sorafenib and Everolimus work at the molecular level. Sorafenib targets specific proteins on cancer cells that help them grow, while Everolimus inhibits a protein that fuels cancer cell growth and proliferation. This combination could potentially block cancer growth more effectively, addressing the disease from multiple angles and offering hope for improved outcomes.

What evidence suggests that this trial's treatments could be effective for thyroid cancer?

Research has shown that sorafenib, which participants in this trial may receive, can significantly slow the progression of advanced thyroid cancer unresponsive to radioactive iodine treatment. It helps patients live longer without disease worsening. Another treatment arm in this trial involves combining sorafenib with everolimus. Studies have found that using both drugs together can enhance their cancer-fighting effects, potentially making them more effective than sorafenib alone. This combined treatment might shrink tumors more and slow cancer growth better than using just one drug. However, this increased effectiveness may also lead to more side effects. ^{2 4 5 6 7}

Who Is on the Research Team?

Eric Sherman, M.D.

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3958462/

Sorafenib in Metastatic Thyroid Cancer: A Systematic Review The data show that treatment with sorafenib in patients with progressive differentiated or medullary thyroid cancer is a promising strategy, but the adverse ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10522190/

Safety and efficacy of sorafenib in patients with advanced ... Sorafenib significantly prolonged progression-free survival in patients with iodine-refractory advanced thyroid cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00984282

Study Details | NCT00984282 | Nexavar® Versus Placebo ... Eligible subjects were randomized 1:1 to sorafenib 800 mg daily or matching placebo. Progression was assessed every 8 weeks by modified RECIST criteria.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2352952022000652

Sorafenib tosylate novel drug delivery systems The USFDA has approved sorafenib tosylate for the treatment of thyroid cancer, kidney cancer, and hepatocellular carcinoma. Conventional formulations of ...

5. oncologynewscentral.com oncologynewscentral.com/drugs/monograph/94784-306001/sorafenib-oral

Sorafenib tosylate: uses, dosing, warnings, adverse events, ... A planned second interim analysis indicated that patients receiving sorafenib had a longer median overall survival than those receiving placebo (10.7 versus 7.9 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39421700/

Safety and efficacy of sorafenib in patients with advanced ... Objective: Sorafenib significantly prolonged progression-free survival in patients with iodine-refractory advanced thyroid cancer. The present study was ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00095693

Sorafenib Tosylate in Treating Patients With Locally ... Sorafenib tosylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor.