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Tyrosine Kinase Inhibitor

Cabozantinib + Nivolumab for Lung Cancer

Phase 2
Waitlist Available
Led By Joel W Neal
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
Creatinine =< 1.5 x ULN OR calculated or measured creatinine clearance >= 50 mL/min/1.73m^2
Patient must have radiographic and/or clinical progression following one line of platinum-based chemotherapy AND one line of prior checkpoint inhibitor immunotherapy
Must not have
Patients must not have specified cardiac, vascular, or thrombotic conditions
Patients must not have specified gastrointestinal, abdominal, or infectious conditions
Timeline
Screening 3 weeks
Treatment Varies
Follow Up every 6 weeks for the first year on study, and then every 12 weeks after year one
Awards & highlights

Summary

This trial is testing cabozantinib with or without nivolumab versus standard chemotherapy in patients with non-squamous non-small cell lung cancer.

Who is the study for?
This trial is for adults with non-squamous non-small cell lung cancer (NSCLC) who've had one round of platinum-based chemo and checkpoint inhibitor immunotherapy. They must have manageable side effects from past treatments, no major organ issues, can swallow pills, and have no severe heart conditions or untreated viral infections. Pregnant individuals or those planning to conceive are excluded.Check my eligibility
What is being tested?
The study tests if cabozantinib alone or combined with nivolumab is more effective than standard chemotherapy in NSCLC treatment. Cabozantinib blocks enzymes needed for tumor growth; nivolumab boosts the immune system's cancer fight. Standard chemo drugs kill or stop cancer cells from growing.See study design
What are the potential side effects?
Cabozantinib may cause liver problems, high blood pressure, mouth sores, hand-foot syndrome (redness and pain on palms/soles), and diarrhea. Nivolumab might lead to immune-related inflammation in organs like lungs or intestines, skin rash, fatigue, and infusion reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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My kidney function, measured by creatinine levels or clearance, is within the required range.
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My cancer progressed after both platinum chemotherapy and immunotherapy.
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I finished my last chemotherapy before the specified time.
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I had hepatitis C but have been treated and cured.
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My tumor does not have EGFR mutations or ALK rearrangements.
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My lung cancer is non-squamous non-small cell type.
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I have not had VEGFR-targeted therapy before.
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My cancer has spread to distant parts of my body.
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I have HIV, am on treatment, and my viral load is undetectable.
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I have chosen a chemotherapy plan for my treatment and haven't used this chemotherapy for metastatic disease before.
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My tumor does not have EGFR mutations or ALK rearrangements.
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I have recovered from side effects of my previous treatment.
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My heart function is classified as class 2B or better according to NYHA.
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I am 18 years old or older.
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I have no ongoing issues from previous radiation treatments.
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I've had one round of chemotherapy and one round of immunotherapy for my cancer.
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I am able to get out of my bed or chair and move around.
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I have HIV, am on treatment, and my viral load is undetectable.
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I am fully active or restricted in physically strenuous activity but can do light work.
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My cancer has grown after at least 2 treatment cycles.
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I have chronic hepatitis B but my viral load is undetectable.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I do not have any heart, blood vessel, or clotting disorders.
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I do not have any serious stomach, gut, or infection issues.
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My cancer has not spread to my brain or spinal cord.
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I haven't had lung inflammation caused by drugs in the last 3 months.
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I haven't had serious stomach or intestinal bleeding in the last 6 months.
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I do not have an active or known history of autoimmune disease.
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I haven't coughed up a significant amount of blood recently.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~every 6 weeks for the first year on study, and then every 12 weeks after year one
This trial's timeline: 3 weeks for screening, Varies for treatment, and every 6 weeks for the first year on study, and then every 12 weeks after year one for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.
Primary outcome measures
Progression-free survival (PFS) for patient population with non-squamous no-small cell lung cancer (NSCLC)
Secondary outcome measures
Best objective response for each arm
Upper arm
Toxicity profile of monotherapy with cabozantinib, and the combination of nivolumab and cabozantinib
Other outcome measures
Agreement between central view and site review in terms of progression-free survival
Correlative biomarker research
The RECIST1.1 response at each time point

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%
Activated Partial Thromboplastin Time Prolonged
15%
Sore Throat
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
8%
Allergic Rhinitis
8%
Generalized Muscle Weakness
8%
Creatinine Increased
8%
Hyponatremia
8%
Flank Pain
8%
Bone Pain
8%
Gastroesophageal Reflux Disease
8%
Chest Pain - Cardiac
8%
Vertigo
8%
Neutrophil Count Decreased
8%
Arthralgia
8%
Syncope
8%
Proteinuria
8%
Pleural Effusion
8%
Nasal Congestion
8%
Pleuritic Pain
8%
Hoarseness
8%
Nail Discoloration
8%
Ventricular Tachycardia
8%
Tinnitus
8%
Gastrointestinal Pain
8%
Floaters
8%
Dysphagia
8%
Blood Bilirubin Increased
8%
Lung Infection
8%
Fever
8%
Depression
8%
Hypersomnia
8%
Hypotension
8%
Productive Cough
8%
Memory Impairment
8%
Anxiety
8%
Cardiac Troponin I Increased
8%
Urinary Incontinence
8%
Pancreatitis
8%
Upper Respiratory Infection
8%
Bruising
8%
Weight Gain
8%
Skin Induration
100%
80%
60%
40%
20%
0%
Study treatment Arm
Cabozantinib

Trial Design

4Treatment groups
Experimental Treatment
Active Control
Group I: Step 2, Arm Z (cabozantinib S-malate, nivolumab)Experimental Treatment5 Interventions
Patients in Step 2, Arm Z receive cabozantinib S-malate PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.
Group II: Step 1, Arm B (cabozantinib S-malate, nivolumab)Experimental Treatment5 Interventions
Patients in Step 1, Arm B receive cabozantinib S-malate PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.
Group III: Step 1, Arm A (cabozantinib S-malate)Experimental Treatment4 Interventions
Patients in Step 1, Arm A receive cabozantinib S-malate PO QD. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may continue to receive therapy after investigator-assessed RECIST 1.1 defined progression, including stable clinical and performance status and have potential for continued clinical benefit. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.
Group IV: Step 1, Arm C (standard chemotherapy)Active Control8 Interventions
Patients in Step 1, Arm C receive ramucirumab IV over 30-60 minutes and docetaxel IV over 1 hour on day 1, or docetaxel IV over 1 hour on days 1 and 8, or gemcitabine hydrochloride IV on days 1 and 8, or paclitaxel IV over 3 hours on day 1, or nab-paclitaxel IV over 30 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity and at the discretion of the treating physician. Patients also undergo ECHO as clinically indicated, CT throughout the trial, and collection of blood on study.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Biospecimen Collection
2004
Completed Phase 2
~1720
Cabozantinib S-malate
2013
Completed Phase 2
~470
Computed Tomography
2017
Completed Phase 2
~2720
Echocardiography
2013
Completed Phase 4
~11670
Nivolumab
2014
Completed Phase 3
~4740

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
Tyrosine Kinase Inhibitors (TKIs) like Cabozantinib block enzymes involved in cancer cell growth, effectively halting their proliferation. Immunotherapy agents such as Nivolumab enhance the immune system's ability to detect and destroy cancer cells by inhibiting proteins that allow cancer to evade immune detection. These mechanisms are vital for lung cancer patients as they guide the selection of targeted treatments, improving the chances of effective management and enhancing quality of life.
A Review of Recent Advances in the Treatment of Elderly and Poor Performance NSCLC.The management of non-small-cell lung cancer: a case history.

Find a Location

Who is running the clinical trial?

National Cancer Institute (NCI)Lead Sponsor
13,748 Previous Clinical Trials
40,959,284 Total Patients Enrolled
Joel W NealPrincipal InvestigatorECOG-ACRIN Cancer Research Group
2 Previous Clinical Trials
128 Total Patients Enrolled

Media Library

Cabozantinib S-malate (Tyrosine Kinase Inhibitor) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04310007 — Phase 2
~5 spots leftby Sep 2024
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