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Squamous Cell Carcinoma of the OropharynxPhase 1/2NCT03370276

Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

A Phase 1/2 study testing Nivolumab and Cetuximab in people with Squamous Cell Carcinoma of the Oropharynx and Squamous Cell Carcinoma of the Larynx, run by H. Lee Moffitt Cancer Center and Research Institute at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to find out if the combination of two established anti-cancer therapies are beneficial in participants with Head and Neck Squamous Cell Carcinoma (HNSCC). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab and Cetuximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
95 participants
Where
3 sitesUnited States
Study dates
20 Dec 2017to 23 Dec 2023
Phase
Phase 1/2
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

  • Participants must have histologically or cytologically confirmed squamous cell carcinoma of oral cavity, oropharynx, paranasal sinuses, nasal cavity, hypopharynx, or larynx. Squamous cell carcinoma of unknown primary in cervical lymph node can be included only if p16 status is positive.
  • Must have recurrent or metastatic HNSCC stage III/IV that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).Patients with persistent disease following radiation therapy administered with a chemotherapy sensitizer may also be included.
  • Must have progressed on at least one prior line of chemotherapy, targeted therapy, palliative radiation, and/or biological therapy regimen for their recurrent and/or metastatic HNSCC. However, if patients are likely to be intolerant to standard first-line systemic chemotherapy, the patients are eligible to enroll to this study as the first-line therapy. Additionally, patients with persistent disease or platinum-refractory recurrent disease may enroll in this study as a first-line therapy.
  • Must NOT have any systemic therapy for recurrent and/or metastatic disease except if given as a part of a multimodality treatment (i.e. re-irradiation and systemic therapy for curable intent of locally recurrent disease).
  • Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as outlined in RECIST version 1.1.
  • Must be ≥ 18 years of age.
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  • Life expectancy of greater than 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Must have normal organ function: Absolute neutrophil count > 1,500/μL; Hemoglobin > 9 g/dL; Platelets > 100,000/μL; Total bilirubin ≤ 1.5 mg/dL X institutional upper limits of normal (ULN); AST (SGOT)/ALT (SGPT) < 3 X institutional ULN (or 5.0 X the ULN in the setting of liver metastasis); Serum creatinine of ≤ 1.5 X ULN or creatinine clearance > 40 mL/minute (using Cockcroft/Gault formula): Female creatinine clearance = (140 - age in years) x weight in kg x 0.8572 x serum creatinine in mg/ dL; Male creatinine clearance = (140 - age in years) x weight in kg x 1.0072 x serum creatinine in mg/dL.
  • Participants, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods). Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Have experienced grade 3 or above skin toxicity from prior Epidermal growth factor receptor (EGFR) inhibiting therapy.
  • Have experienced grade 3 or above toxicity from prior anti-PD1 therapy.
  • Have p16 negative squamous cell carcinoma of unknown primary in cervical lymph node.
  • Patients with primary nasopharynx or salivary gland cancers.
  • Patients who have had chemotherapy, biological therapy or definitive radiation within 4 weeks of the study enrollment or those who have not recovered from adverse events to ≤ Grade 1 due to agents administered more than 4 weeks earlier.
  • Had undergone any major surgery within 4 weeks of study enrollment.
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  • Had undergone any palliative radiation within 2 weeks of study enrollment.
  • Have had other investigational agents within 4 weeks or 5 half-lives, whichever is shorter, of the study enrollment.
  • Have known leptomeningeal metastases or untreated or symptomatic brain metastases. Treated, asymptomatic brain metastasis can be included.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease requiring systemic steroids, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Have clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency.
  • Have uncontrolled or poorly controlled hypertension (>180 mmHg systolic or > 130 mmHg diastolic) at the time of enrollment.
  • Prior treatment with a combination of cetuximab and a PD-1/PD-L1 inhibitor. Prior treatment with cetuximab or a PD-1/PD-L1 inhibitor is allowed as long as not previously given in combination.
  • A history of allergic reactions attributed to compounds of chemical or biologic composition similar to those of cetuximab and/or nivolumab.
  • Pregnant or breast-feeding.
  • Known active HIV, Hep B, or Hep C infection. If not clinically indicated, the patients do not need to be tested.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Emory University School of Medicine

    Atlanta, Georgia, 30322

  • The Ohio State University

    Columbus, Ohio, 43210

  • H. Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase I/II Study of Concurrent Cetuximab and Nivolumab in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

The purpose of this study is to find out if the combination of two established anti-cancer therapies are beneficial in participants with Head and Neck Squamous Cell Carcinoma (HNSCC). Specifically, investigators want to determine if the combination of Cetuximab and nivolumab can help people with advanced cases of HNSCC. Both cetuximab and nivolumab have been used separately to treat HNSCC and are Food and Drug Administration (FDA) approved in this type of cancer.

Read the detailed description

PHASE I: Participants will be enrolled sequentially and treated at Dose Level 1, or Dose Level -1, every 2 weeks for 12 cycles or until discontinuation.

Each cycle is 4 weeks. Cetuximab is given alone in lead-in period at Day -14 before Cycle 1 only. In all subsequent doses starting Cycle 1 Day 1, nivolumab and cetuximab will be given concurrently. Dose limiting toxicity (DLT) assessment will be performed during Cycle 1 and will start with the initiation of the combination of cetuximab and nivolumab (4 weeks).

PHASE II: Once the maximum tolerated dose (MTD) or the recommended phase II dose of cetuximab is determined in Phase I, accrual to the phase II will begin.

FOLLOW-UP: Participants will be followed for 2 years from End of Treatment. The imaging studies will be performed every 8 weeks (2 cycles) of the treatments during Cycle 1-6 and then every 12 weeks during Cycle 7-12 as per standard of care. Patient will be followed by treating physicians as per standard of care.

Being tested
Nivolumab, Cetuximab
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Neoplasms, Squamous Cell

What participants receive

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

  • NivolumabDrug

    Also called Opdivo

    Nivolumab intravenously (IV) at 240 mg as outlined in the treatment arms.

  • CetuximabDrug

    Also called Erbitux

    Cetuximab intravenously (IV) at 500 mg/m^2 or 250 mg/m^2 as outlined in the treatment arms.

Study groups in NCT03370276
Study groupRoleWhat they receive
Phase I - Affiliate Sites OnlyExperimentalNivolumab and dose escalation of Cetuximab. Dose Level 1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m^2; Nivolumab 240 mg. Dose Level -1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 250 mg/m^2; Nivolumab 240 mg.
Receives: Drug: Nivolumab; Drug: Cetuximab
Phase I - Moffitt Site OnlyExperimentalNivolumab and dose escalation of Cetuximab. Dose Level 1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 500 mg/m^2; Nivolumab 240 mg. Dose Level -1: Lead-in Day -14 before Cycle 1 only: Cetuximab 500 mg/m^2; Nivolumab - none. Cycle 1 Day 1 and all subsequent doses every 2 weeks (Q2W): Cetuximab 250 mg/m^2; Nivolumab 240 mg.
Receives: Drug: Nivolumab; Drug: Cetuximab
Phase II - Affiliate Sites OnlyExperimentalNivolumab and Cetuximab at recommended Phase II dose (RP2D).
Receives: Drug: Nivolumab; Drug: Cetuximab
Phase II - Moffitt Site OnlyExperimentalNivolumab and Cetuximab at recommended Phase II dose (RP2D).
Receives: Drug: Nivolumab; Drug: Cetuximab

What is being measured

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

  1. Phase I: Maximum Tolerated Dose

    Maximum Tolerated Dose (MTD).. The target Dose Limiting Toxicity (DLT) rate is <25%. The MTD will be defined as the dose of cetuximab and nivolumab in which <1 of 3 patients experience a DLT or <2 of 6 patients experience a DLT with the next higher dose having at least 2 patients experiencing a DLT. The MTD is the highest dose at which at most 1 of 6 patients has a DLT. This study will utilize the Cancer Therapy Evaluation Program CTCAE version 4.1 for toxicity and event reporting. Dose-limiting toxicities will be observed until patients have completed Cycle 1 (4 weeks).

    Measured: Up to 12 months

  2. Phase II: Overall Survival (OS)

    One year overall survival of concurrent cetuximab and nivolumab in patients with recurrent and/or metastatic HNSCC. OS: The length of time from the start of treatment until death by any cause.

    Measured: Up to 24 months

Secondary outcomes (3)

  1. Overall Response Rate (ORR)

    Complete Response (CR): The disappearance of all measurable lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameters of measureable lesions, taking as reference the baseline sum longest diameter. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s). Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 6 weeks.

    Measured: Up to 48 months

  2. Progression Free Survival (PFS)

    Progressive Disease (PD): At least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).

    Measured: at 12 months

  3. Number of Study Treatment Related Adverse Events

    Related adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) V4.1. An adverse event (AE) is defined as any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a patient in a clinical investigation who received a pharmaceutical product.

    A serious adverse event (SAE) is defined as any AE that results in death, is immediately life-threatening, results in persistent or significant disability/incapacity, requires or prolongs patient hospitalization, is a congenital anomaly/birth defect, or is to be deemed serious for any other reason if it is an important medical event when based on appropriate medical judgement that may jeopardize the patient and may require medical or surgical intervention to prevent one of the other outcomes listed in the above definitions.

    Measured: Up to 48 months

Timeline

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

  1. First posted12 Dec 2017
  2. Study start20 Dec 2017
  3. Primary completion4 Sep 2021
  4. Study completion23 Dec 2023

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
95 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03370276
Sponsor's protocol ID
MCC-19178
Status last verified
Mar 2026
First submitted
7 Dec 2017
Last updated
2 Apr 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Park R, Rind F, Kristoff T, Li J, Schell M, Slebos RJC, Thatikonda S, Chaudhary R, Biernacki MI, Meshkovska Y, Kaldas D, Kim HS, Farinhas J, Hernandez-Prera J, Kirtane K, Hall MS, Amelio AL, Rocco JW, Bhateja P, Steuer C, Bonomi M, Saba NF, Chung CH. Evaluation of Neutrophil to Lymphocyte Ratio in Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma Treated With a Combination of Cetuximab and Nivolumab in a Phase II Clinical Trial. Am J Clin Oncol. 2026 Apr 1;49(4):176-187. doi: 10.1097/COC.0000000000001255. Epub 2025 Sep 4.

    PubMed 40905435

  • Wang X, Muzaffar J, Kirtane K, Song F, Johnson M, Schell MJ, Li J, Yoder SJ, Conejo-Garcia JR, Guevara-Patino JA, Bonomi M, Bhateja P, Rocco JW, Steuer CE, Saba NF, Chung CH. T cell repertoire in peripheral blood as a potential biomarker for predicting response to concurrent cetuximab and nivolumab in head and neck squamous cell carcinoma. J Immunother Cancer. 2022 Jun;10(6):e004512. doi: 10.1136/jitc-2022-004512.

    PubMed 35676062

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab and Cetuximab in people with Squamous Cell Carcinoma of the Oropharynx and Squamous Cell Carcinoma of the Larynx, run by H. Lee Moffitt Cancer Center and Research Institute at 3 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 11 inclusion and 17 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: finished, as of the sponsor's last update on 2 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 20 Dec 2022). 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?

Phase I: Maximum Tolerated Dose (time frame: Up to 12 months). The study lists 2 primary outcomes in all. 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 NCT03370276, which also lists 2 linked publications.

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 2 Apr 2026.

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