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Metastatic Head and Neck CarcinomaPhase 2NCT03468218

Pembrolizumab & Cabozantinib in Patients With Head and Neck Squamous Cell Cancer

A Phase 2 study testing Cabozantinib and Pembrolizumab in people with Metastatic Head and Neck Carcinoma and Paranasal Sinus Squamous Cell Carcinoma, run by Emory University at 2 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This phase II trial studies how well pembrolizumab and cabozantinib in treating patients with head and neck squamous cell cancer that has come back or spread to other places in the body and cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cabozantinib and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
2 sitesUnited States
Study dates
18 Sep 2018to 29 Oct 2026
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The subject has a histologic or cytologic diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, paranasal sinuses, hypopharynx, nasopharynx, or larynx; squamous cell carcinoma of unknown primary in cervical lymph node can be included only if human papillomavirus (HPV) status is positive
  • Patients must have refractory, recurrent or metastatic disease, which is deemed to be inoperable
  • In case patients received prior systemic therapy within the definitive or metastatic setting, disease progression must be documented following prior therapy; this can be in the recurrent or metastatic setting or in the concurrent setting
  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the investigator
  • A maximum of one prior radiotherapy regimen, curative or palliative, to the head and neck is allowed; if the radiation is combined with chemotherapy, a minimum of 4 months must elapse between the end of radiotherapy and registration; if the radiation is given alone, a minimum of 8 weeks must elapse between the end of radiotherapy and registration; a minimum of 3 weeks must elapse between prior radiation to other areas and registration; treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation
  • The subject has had an assessment of all known disease sites eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan or positron emission tomography (PET)/CT scan as appropriate, within 28 days before the first dose of cabozantinib
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  • Life expectancy of greater than 3 months
  • The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Recovery to baseline or ≤ grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy
  • Within 7 days before the first dose of cabozantinib: The absolute neutrophil count (ANC) ≥ 1000/mm³ without colony stimulating factor support
  • Within 7 days before the first dose of cabozantinib: Platelets ≥ 100,000/mm³
  • Within 7 days before the first dose of cabozantinib: Hemoglobin ≥ 9 g/dL
  • Within 7 days before the first dose of cabozantinib: Bilirubin ≤ 1.5 x the upper limit of normal (ULN); for subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL
  • Within 7 days before the first dose of cabozantinib: Serum albumin ≥ 2.8 g/dl
  • Within 7 days before the first dose of cabozantinib: Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min; for creatinine clearance estimation, the Cockcroft and Gault equation should be used
  • Within 7 days before the first dose of cabozantinib: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN
  • Within 7 days before the first dose of cabozantinib: Lipase < 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis
  • Within 7 days before the first dose of cabozantinib: Urine protein/creatinine ratio (UPCR) ≤ 1
  • Within 7 days before the first dose of cabozantinib: Serum phosphorus, calcium, magnesium and potassium ≥ lower limit of normal (LLN)
  • The subject is capable of understanding and complying with the protocol requirements and has signed the informed consent document
  • Sexually active subjects (men and women) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used; all subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s)
  • Female subjects of childbearing potential must not be pregnant at screening; females of childbearing potential are defined as premenopausal females capable of becoming pregnant (ie, females who have had any evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy); however, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons

Who cannot join

  • Patients who have HPV negative squamous cell carcinoma of unknown primary in cervical lymph node
  • The subject has received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (eg, cytokines or antibodies) within 4 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment
  • Prior treatment with cabozantinib or pembrolizumab
  • Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment; systemic treatment with radionuclides within 6 weeks before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
  • Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment
  • The subject has received any other type of investigational agent within 28 days or 5 half-lives, whichever is shorter, before the first dose of study treatment
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  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before the first dose of study treatment; eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment
  • The subject has prothrombin time (PT)/institutional normalized ratio (INR) or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment
  • Concomitant anticoagulation at therapeutic doses with oral anticoagulants (eg, warfarin, direct thrombin and factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel)
  • Note: Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (< 1 mg/day), and low dose, low molecular weight heparins (LMWH) are permitted; anticoagulation with therapeutic doses of LMWH is allowed in subjects who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
  • The subject has experienced any of the following:
  • Clinically-significant GI bleeding within 6 months before the first dose of study treatment
  • Hemoptysis of ≥ 0.5 teaspoon (2.5 ml) of red blood within 3 months before the first dose of study treatment
  • Any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment
  • The subject has radiographic evidence of cavitating pulmonary lesion(s)
  • The subject has tumor invading or encasing any major blood vessels
  • The subject has evidence of tumor invading the gastrointestinal (GI) tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of cabozantinib
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders including:
  • Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening;
  • Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment;
  • Any history of congenital long QT syndrome;
  • Any of the following within 6 months before the first dose of study treatment:
  • Unstable angina pectoris;
  • Clinically-significant cardiac arrhythmias;
  • Stroke (including transient ischemic attack (TIA), or other ischemic event);
  • Myocardial infarction;
  • GI disorders particularly those associated with a high risk of perforation or fistula formation including:
  • Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction
  • Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months before randomization
  • Note: Complete healing of an intra-abdominal abscess must be confirmed prior to randomization. Also no pre-existing fistula of head and neck area; no pre-existing osteonecrosis of jaw (ONJ)
  • Other clinically significant disorders that would preclude safe study participation
  • Major surgery within 12 weeks before the first dose of study treatment; complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment; minor surgery (including uncomplicated tooth extractions) within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior surgery are not eligible
  • Corrected QT interval by Fridericia's formula (QTcF) > 500 msec within 1 month before the first dose of study treatment
  • Three electrocardiography (ECG)s must be performed for eligibility determination; if the average of these three consecutive results for QTcF is ≤ 500 msec, the subject meets eligibility in this regard
  • Pregnant or lactating females
  • Inability to swallow intact tablets or inability to take pembrolizumab or cabozantinib
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations
  • Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 1 year post diagnosis; patients with a prior history of squamous cell or basal carcinoma of the skin or in situ cervical cancer must have been curatively treated

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase II Trial of Pembrolizumab and Cabozantinib in Patients With RM SCCHN

This phase II trial studies how well pembrolizumab and cabozantinib in treating patients with head and neck squamous cell cancer that has come back or spread to other places in the body and cannot be removed by surgery. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Cabozantinib may stop the growth of tumor cells by blocking some of the pathways needed for cell growth. Giving pembrolizumab and cabozantinib may improve the chances of tumor response in patients with head and neck squamous cell cancer.

Read the detailed description

PRIMARY OBJECTIVE:

To estimate the overall response rate (ORR) of patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN) who receive the combination of pembrolizumab and cabozantinib.

SECONDARY OBJECTIVES:

  • To estimate the progression-free survival (PFS) of patients treated with the combination of pembrolizumab and cabozantinib.
  • To further define the toxicities associated with these regimens in patients with SCCHN.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and cabozantinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up to 2 years.

Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabozantinibDrug

    Also called Cabometyx, Cometriq

    Given PO

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT03468218
Study groupRoleWhat they receive
Treatment (pembrolizumab, cabozantinib)ExperimentalPatients receive pembrolizumab IV over 30 minutes on day 1 and cabozantinib PO QD on days 1-21. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Cabozantinib; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    Will assess the proportion of subjects with partial response or complete response as defined by Response Evaluation Criteria in Solid Tumors version 1.1 response criteria. ORR will be calculated with 95% confidence interval by binomial distribution. The ability of biomarkers to predict ORR will be estimated by chi-square test and/or logistic regression model.

    Measured: Up to 2 years after treatment start

Secondary outcomes (1)

  1. Progression Free Survival (PFS)

    The median PFS will be estimated by Kaplan-Meier method along with 95% confidence interval. The biomarker association with PFS will be assessed by the Kaplan-Meier method, log-rank test, and Cox model.

    Measured: Duration from date of treatment start to the date of objectively documented progression or death due to any cause, whichever status is recorded first, assessed up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2018
  2. Study start18 Sep 2018
  3. Primary completion2 May 2022
  4. Study completion29 Oct 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03468218
Sponsor's protocol ID
IRB00100269
Other IDs
NCI-2017-02419, Winship4234-17, P30CA138292
Status last verified
Jan 2026
First submitted
10 Mar 2018
Last updated
23 Jan 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Saba NF, Steuer CE, Ekpenyong A, McCook-Veal A, Magliocca K, Patel M, Schmitt NC, Stokes W, Bates JE, Rudra S, Remick J, McDonald M, Abousaud M, Tan AC, Fadlullah MZH, Chaudhary R, Muzaffar J, Kirtane K, Liu Y, Chen GZ, Shin DM, Teng Y, Chung CH. Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial. Nat Med. 2023 Apr;29(4):880-887. doi: 10.1038/s41591-023-02275-x. Epub 2023 Apr 3.

    PubMed 37012550

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib and Pembrolizumab in people with Metastatic Head and Neck Carcinoma and Paranasal Sinus Squamous Cell Carcinoma, run by Emory University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to 2 years after treatment start). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03468218, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2026.

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