What side effects are associated with this type of intervention?

The most common treatments for thyroid cancer, such as Cabozantinib (a tyrosine kinase inhibitor), Nivolumab (a PD-1 inhibitor), and Ipilimumab (a CTLA-4 inhibitor), have notable side effects. Cabozantinib often causes hypertension, diarrhea, fatigue, and hand-foot syndrome. Nivolumab can lead to immune-related adverse events like colitis, hepatitis, pneumonitis, and various endocrinopathies. Ipilimumab is associated with severe colitis, dermatitis, and endocrinopathies. When these therapies are combined, the risk and severity of these side effects may increase.

What prior FDA approvals exist?

For the treatment of thyroid cancer, the FDA has approved several tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib, which target the vascular endothelial growth factor receptor (VEGFR) among other pathways. These drugs are used for differentiated thyroid cancer that is refractory to radioactive iodine treatment. Additionally, the PD-1 inhibitor pembrolizumab has been approved for use in certain cases of thyroid cancer with high tumor mutational burden. While specific approvals for the combination of cabozantinib, nivolumab, and ipilimumab in thyroid cancer are not mentioned, these types of drugs are being actively studied in clinical trials for their potential efficacy in this and other cancers.

What other types of research exist?

Promising novel alternatives for thyroid cancer treatment in 2024 may include new tyrosine kinase inhibitors (TKIs) targeting different pathways, next-generation immune checkpoint inhibitors, and combination therapies involving novel agents such as lenvatinib with pembrolizumab. Additionally, emerging therapies targeting specific genetic mutations or molecular alterations in thyroid cancer could offer new treatment options.

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Tyrosine Kinase Inhibitor

Cabozantinib + Nivolumab + Ipilimumab for Thyroid Cancer

Phase 2

Waitlist Available

Led By Bhavana Konda

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include diarrhea, high blood pressure, fatigue, liver issues like hepatitis, mouth sores, hand-foot syndrome (redness and pain in hands/feet), hormone gland problems (like thyroid dysfunction), skin rash or itching.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Objective response rate

Secondary study objectives

Incidence of adverse events (AEs)

Overall survival

Progression-free survival

Other study objectives

Circulating myeloid-derived suppressor cells

PD-1/PD-L1 expression in the primary/metastatic tumor in biopsies

Peripheral blood mononuclear cell (cell)

+4 more

Side effects data

From 2019 Phase 2 trial • 13 Patients • NCT02315430

85%

Fatigue

77%

Nausea

62%

Dysgeusia

62%

Vomiting

54%

Alkaline Phosphatase Increased

54%

Aspartate Aminotransferase Increased

54%

Mucositis Oral

54%

Abdominal Pain

46%

Hypertension

46%

Anorexia

38%

Alanine Aminotransferase Increased

38%

Thromboembolic Event

38%

Anemia

38%

Diarrhea

38%

Constipation

38%

Cough

38%

Weight Loss

38%

Dyspnea

31%

Hypomagnesemia

31%

Back Pain

31%

Lipase Increased

31%

Hypoalbuminemia

23%

Hypophosphatemia

23%

Hyperglycemia

23%

Dizziness

23%

Palmar-Plantar Erythrodysesthesia Syndrome

23%

Alopecia

23%

Hypothyroidism

23%

Pain In Extremity

23%

Oral Pain

23%

Pain

23%

Headache

15%

Sore Throat

15%

Activated Partial Thromboplastin Time Prolonged

15%

Myalgia

15%

Bloating

15%

White Blood Cell Decreased

15%

Insomnia

15%

Dry Mouth

15%

Dyspepsia

15%

Dehydration

15%

Hypocalcemia

15%

Dry Skin

15%

Flushing

15%

Peripheral Sensory Neuropathy

15%

Abdominal Distension

15%

Platelet Count Decreased

Allergic Rhinitis

Generalized Muscle Weakness

Creatinine Increased

Hyponatremia

Flank Pain

Bone Pain

Gastroesophageal Reflux Disease

Chest Pain - Cardiac

Vertigo

Neutrophil Count Decreased

Arthralgia

Syncope

Proteinuria

Pleural Effusion

Nasal Congestion

Pleuritic Pain

Hoarseness

Nail Discoloration

Ventricular Tachycardia

Tinnitus

Gastrointestinal Pain

Floaters

Dysphagia

Blood Bilirubin Increased

Lung Infection

Fever

Depression

Hypersomnia

Hypotension

Productive Cough

Memory Impairment

Anxiety

Cardiac Troponin I Increased

Urinary Incontinence

Pancreatitis

Upper Respiratory Infection

Bruising

Weight Gain

Skin Induration

100%

80%

60%

40%

20%

Study treatment Arm

Cabozantinib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (cabozantinib S-malate, nivolumab, ipilimumab)Experimental Treatment6 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Nivolumab

2015

Completed Phase 3

~4010

Biospecimen Collection

2004

Completed Phase 3

~2030

Cabozantinib S-malate

2013

Completed Phase 2

~590

Computed Tomography

2017

Completed Phase 2

~2790

Ipilimumab

2015

Completed Phase 3

~3420

Magnetic Resonance Imaging

2017

Completed Phase 3

~1180

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for thyroid cancer, such as Cabozantinib, Nivolumab, and Ipilimumab, work through distinct mechanisms that target tumor growth and enhance immune response. Cabozantinib, a tyrosine kinase inhibitor, blocks enzymes necessary for tumor growth and angiogenesis, effectively cutting off the tumor's blood supply. Nivolumab, a PD-1 inhibitor, prevents cancer cells from evading the immune system, allowing T-cells to attack the tumor. Ipilimumab, a CTLA-4 inhibitor, boosts T-cell activation and proliferation, further enhancing the immune response against cancer cells. These targeted therapies are crucial for thyroid cancer patients as they offer more effective and personalized treatment options, potentially improving survival rates and quality of life.

Narrative review of pembrolizumab for the treatment of esophageal cancer: evidence and outlook.Immunotherapies in Early and Advanced Renal Cell Cancer.