What is the mechanism of action of this treatment?

Nivolumab is an immunotherapy that works by blocking the PD-1 pathway, thereby enhancing the immune system's ability to attack melanoma cells. Cabozantinib inhibits tyrosine kinases, which are enzymes that promote tumor growth and metastasis. For melanoma patients, these treatments are significant because they offer targeted approaches to combat the cancer, potentially leading to more effective and durable responses compared to traditional therapies.

What side effects are associated with this type of intervention?

Common treatments for melanoma, such as nivolumab and cabozantinib, have distinct side effect profiles. Nivolumab, an immunotherapy with monoclonal antibodies, often causes immune-related adverse events including skin rashes, colitis, hepatitis, and endocrine disorders. Cabozantinib, which inhibits enzymes and proteins, can lead to hypertension, diarrhea, fatigue, and hand-foot syndrome. When used in combination, these treatments may increase the likelihood of experiencing these side effects.

What prior FDA approvals exist?

The FDA has approved several treatments for melanoma, particularly focusing on immunotherapy and targeted therapies. Nivolumab, a monoclonal antibody that enhances the immune system's ability to fight cancer, has been approved for use alone or in combination with ipilimumab. Pembrolizumab, another PD-1 inhibitor, is also approved for melanoma. For targeted therapy, drugs like vemurafenib and dabrafenib, which inhibit the BRAF protein, and trametinib, which inhibits MEK, have been approved. Cabozantinib, which inhibits multiple tyrosine kinases, is being studied in combination with nivolumab for its potential to prevent melanoma recurrence.

What other types of research exist?

Promising novel alternatives for melanoma treatment in 2024 include: 1) Pembrolizumab (another PD-1 inhibitor) which has shown efficacy in various trials. 2) Relatlimab combined with Nivolumab, targeting both PD-1 and LAG-3 pathways. 3) Atezolizumab (a PD-L1 inhibitor) combined with Bevacizumab, which has shown potential in renal cell carcinoma and may be applicable to melanoma. 4) Lenvatinib combined with Pembrolizumab, targeting multiple pathways including VEGFR and PD-1. These alternatives offer different mechanisms of action and combination strategies that may provide effective treatment options for melanoma patients.

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Checkpoint Inhibitor

Nivolumab + Cabozantinib for Melanoma

Phase 2

Recruiting

Led By Alexander N Shoushtari

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 5 years

Summary

This trial tests if nivolumab and cabozantinib can help patients with mucosal melanoma. Nivolumab boosts the immune system, while cabozantinib stops cancer cells from growing. The goal is to prevent the cancer from coming back or spreading. Nivolumab and cabozantinib have shown efficacy in treating various cancers, including melanoma and renal cell carcinoma.

Who is the study for?

Adults who've had surgery for mucosal melanoma without distant metastases can join. They must have certain types of primary lesions or lymph node involvement, no recent heart issues, infections, or other cancers needing treatment. Pregnant/nursing women and those with severe liver disease, autoimmune conditions on steroids, untreated spinal cord compression, bleeding disorders or active infections are excluded.

What is being tested?

The trial is testing if nivolumab combined with cabozantinib prevents mucosal melanoma from returning after surgery. Nivolumab boosts the immune system to fight cancer while cabozantinib blocks enzymes that help tumor cells grow.

What are the potential side effects?

Possible side effects include fatigue, high blood pressure, diarrhea, mouth sores and hand-foot syndrome (redness and pain in hands/feet). Liver problems might occur due to cabozantinib's effect on proteins involved in cell growth.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 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

Recurrence free survival (RFS)

Secondary study objectives

Duration of response (Arm 3)

Incidence of adverse events

Overall survival (OS)

+2 more

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Arm 3 (nivolumab, cabozantinib)Experimental Treatment7 Interventions

Patients receive nivolumab IV over 30 minutes and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 26 cycle in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo stool sample collection at baseline, and blood and tissue sample collection at baseline and on the trial.

Group II: Arm 1 (nivolumab, cabozantinib)Experimental Treatment7 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo stool sample collection at baseline, and blood and tissue sample collection at baseline and on the trial.

Group III: Arm 2 (nivolumab, placebo)Active Control7 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 and placebo PO QD of each cycle. Treatment repeats every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and as clinically indicated throughout the trial. Patients may undergo CT, MRI, or PET/CT at baseline, CT and MRI may be repeated every 6 months on study. Additionally, patients may undergo stool sample collection at baseline, and blood and tissue sample collection at baseline and on the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Magnetic Resonance Imaging

2017

Completed Phase 3

~1160

Nivolumab

2015

Completed Phase 3

~4010

Computed Tomography

2017

Completed Phase 2

~2740

Echocardiography

2013

Completed Phase 4

~11580

Positron Emission Tomography

2011

Completed Phase 2

~2200

Biospecimen Collection

2004

Completed Phase 3

~2020

Cabozantinib S-malate

2013

Completed Phase 2

~490

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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

Nivolumab is an immunotherapy that works by blocking the PD-1 pathway, thereby enhancing the immune system's ability to attack melanoma cells. Cabozantinib inhibits tyrosine kinases, which are enzymes that promote tumor growth and metastasis. For melanoma patients, these treatments are significant because they offer targeted approaches to combat the cancer, potentially leading to more effective and durable responses compared to traditional therapies.