Cabozantinib + Nivolumab + Ipilimumab for Thyroid Cancer

Recruiting at 35 trial locations

Overseen By Prakash C. Neupane

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Oral anticoagulants, Immunosuppressants

Disqualifiers: Other malignancy, Autoimmune 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 14

Duration: 6 months

9 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial studies how well a combination of cabozantinib, nivolumab, and ipilimumab works in patients with thyroid cancer that hasn't responded to other treatments. Cabozantinib stops cancer growth by blocking certain enzymes, while nivolumab and ipilimumab help the immune system fight the cancer.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you cannot take certain medications like strong CYP3A4 inducers or require systemic corticosteroids above a certain dose. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

What data supports the effectiveness of the drug combination Cabozantinib, Nivolumab, and Ipilimumab for thyroid cancer?

Cabozantinib has been shown to significantly slow down the progression of medullary thyroid cancer, a rare type of thyroid cancer, in patients with advanced stages of the disease. It is also approved for treating differentiated thyroid cancer that has worsened after other treatments. While specific data on the combination with Nivolumab and Ipilimumab for thyroid cancer is limited, Cabozantinib's effectiveness in similar conditions suggests potential benefits. ^{1 2 3 4 5}

Is the combination of Cabozantinib, Nivolumab, and Ipilimumab safe for humans?

Cabozantinib has been used in treating medullary thyroid cancer and has shown some side effects like gastrointestinal issues, bleeding, high blood pressure, and blood clots, which are typical for its type of drug. These side effects were generally managed with supportive care and dose adjustments. ^{1 3 5 6 7}

What makes the drug combination of Cabozantinib, Nivolumab, and Ipilimumab unique for thyroid cancer?

This drug combination is unique because it combines Cabozantinib, which targets multiple pathways involved in cancer growth, with Nivolumab and Ipilimumab, which are immunotherapies that help the immune system attack cancer cells. This approach is novel for thyroid cancer, especially for cases that have progressed after other treatments. ^{2 3 4 5 8}

Research Team

Bhavana Konda

Principal Investigator

Ohio State University Comprehensive Cancer Center LAO

Eligibility Criteria

Adults with advanced differentiated thyroid cancer that's resistant to radioactive iodine and has worsened after VEGFR-targeted therapy. They must have measurable disease, not be pregnant, agree to use contraception, and be able to swallow pills. Excludes those with certain other cancers within the last 2 years or specific health conditions.

Inclusion Criteria

I have someone legally authorized to make decisions for me due to my impaired decision-making capacity.

I have HIV, am on treatment, and my viral load is undetectable.

My thyroid cancer does not respond to radioactive iodine treatment.

Exclusion Criteria

I am not on any medications that are not allowed in the study.

My cancer has not spread to major blood vessels or the GI tract.

I do not have untreated brain or spinal cord cancer spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Pre-Treatment

Patients receive cabozantinib S-malate orally once daily on days -14 to -1 prior to cycle 1

2 weeks

1 visit (in-person)

Treatment

Patients receive cabozantinib S-malate, nivolumab, and ipilimumab. Treatment repeats every 42 days for cycles 1-4 and every 28 days for subsequent cycles.

6 months

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 12 weeks

Treatment Details

Interventions

• Cabozantinib S-malate
• Ipilimumab
• Nivolumab

Trial Overview The trial is testing a combination of three drugs: Cabozantinib (blocks enzymes for cell growth), Nivolumab, and Ipilimumab (both boost the immune system against cancer). It aims to see if this trio is more effective than standard chemotherapy treatments for this type of thyroid cancer.

Participant Groups

Group I: Treatment (cabozantinib S-malate, nivolumab, ipilimumab) Experimental Treatment 6 Interventions

Patients receive cabozantinib S-malate PO QD on days -14 to -1 prior to cycle 1, days 1-42 of cycles 1-4 and days 1-28 of subsequent cycles. Patients also receive nivolumab IV over 30 minutes on days 1, 15, and 29 of cycles 1-4 and day 1 of subsequent cycles and ipilimumab IV over 90 minutes on day 1 of cycles 1-4. Treatment repeats every 42 days for cycles 1-4 and every 28 days for subsequent cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI during screening, and blood sample collection throughout the study.

Cabozantinib S-malate is already approved in United States, European Union for the following indications:

Approved in United States as Cabometyx for:

• Advanced renal cell carcinoma (RCC)
• Hepatocellular carcinoma (HCC)
• Locally advanced or metastatic differentiated thyroid cancer (DTC)

Approved in United States as Cometriq for:

• Medullary thyroid cancer

Approved in European Union as Cabometyx for:

• Advanced renal cell carcinoma (RCC)
• Hepatocellular carcinoma (HCC)
• Locally advanced or metastatic differentiated thyroid cancer (DTC)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 346 patients receiving cabozantinib (CABO) as second-line therapy after various first-line treatments, the median overall survival was 21.4 months for those who previously received ipilimumab-nivolumab (IPI-NIVO), indicating that CABO is effective regardless of the initial treatment.

The median time to treatment failure for CABO was 7.6 months, suggesting that it provides a clinically meaningful benefit as a second-line option after different first-line therapies, including immunotherapy and VEGF inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CABOSEQ: The Effectiveness of Cabozantinib in Patients With Treatment Refractory Advanced Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Navani, V., Wells, JC., Boyne, DJ., et al.[2023]

Cabozantinib (Cabometyx) has received approval for the treatment of locally advanced or metastatic differentiated thyroid cancer that has not responded to previous therapies targeting vascular endothelial growth factor receptors.

This approval highlights Cabozantinib's efficacy in addressing a specific type of thyroid cancer that has progressed after other treatments, providing a new option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indication for Cabozantinib. Aschenbrenner, DS.[2023]

In a real-world analysis of adverse events from two combination therapies for advanced renal cell carcinoma, cabozantinib (CAB) plus nivolumab (NIVO) showed higher incidence rates of seven types of toxicities compared to ipilimumab (IPI) plus NIVO.

Conversely, IPI + NIVO was associated with higher rates of three types of toxicities and had a greater incidence of serious adverse events, suggesting that both therapies have distinct safety profiles that can guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. Blas, L., Shiota, M., Tsukahara, S., et al.[2023]

In a phase 3 trial involving 855 patients with untreated advanced renal-cell carcinoma, the combination of cabozantinib with nivolumab and ipilimumab significantly improved progression-free survival compared to nivolumab and ipilimumab alone, with a 12-month progression-free survival rate of 57% versus 49%.

However, the experimental group experienced a higher incidence of severe adverse events (grade 3 or 4) at 79%, compared to 56% in the control group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. Choueiri, TK., Powles, T., Albiges, L., et al.[2023]

References

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

Cabozantinib: a review of its use in patients with medullary thyroid cancer. [2022]

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

Pharmaceutical approval update. [2021]

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

CABOSEQ: The Effectiveness of Cabozantinib in Patients With Treatment Refractory Advanced Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). [2023]

4. England pubmed.ncbi.nlm.nih.gov

Cabozantinib and vandetanib for unresectable locally advanced or metastatic medullary thyroid cancer: a systematic review and economic model. [2022]

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

New Indication for Cabozantinib. [2023]

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

Adverse Events of Cabozantinib Plus Nivolumab Versus Ipilimumab Plus Nivolumab. [2023]

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

Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. [2023]

8. France pubmed.ncbi.nlm.nih.gov

[Cabozantinib: Mechanism of action, efficacy and indications]. [2022]