Squamous Cell Cancers of the Head and NeckPhase 2NCT02979977
Dual Inhibition of EGFR With Afatinib and Cetuximab in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck
A Phase 2 study testing cetuximab and afatinib in people with Squamous Cell Cancers of the Head and Neck, run by Yale University at 1 site in United States.
Trial summary
This is a single arm Phase II study for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with an immune checkpoint inhibitor. The primary objective is to evaluate the efficacy of the combination of cetuximab and afatinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Squamous Cell Cancers of the Head and Neck
- What is being tested?
- cetuximab and afatinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Mar 2017to 18 Jan 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
- Histologically confirmed squamous cell carcinoma of the head and neck that is metastatic, recurrent or locally advanced and not treatable with curative intent.
- Previous treatment with a platinum-based regimen or immune checkpoint inhibitor or both.2-week washout period prior to treatment start will be required.
- Patients who have experienced progression of disease within 6 months following completion of a platinum-based chemoradiation in the definitive or adjuvant setting will be permitted.
- Prior cetuximab permitted if it was given as part of multi-modality therapy for initial treatment of locally advanced disease.
- Measurable disease based on RECIST v 1.1. Baseline measurements and evaluations must be obtained within 4 weeks of enrollment. Disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy.
- ECOG performance status ≤2
Show all 16Show fewer
- Adequate organ function, defined as all of the following:
- Hemoglobin ≥ 8 g/dl.
- Absolute neutrophil count (ANC) ≥1000 / mm3.
- Platelet count ≥75,000 / mm3.
- Estimated creatinine clearance > 45ml / min.
- Total Bilirubin ≤ 1.5 times upper limit of (institutional/central) normal (Patients with Gilbert's syndrome total bilirubin must be ≤4 times institutional upper limit of normal).
- Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ three times the upper limit of (institutional/central) normal (ULN) (if related to liver metastases ≤ five times ULN).
- Ability to understand and the willingness to sign a written informed consent that is consistent with ICH-GCP guidelines.
- Negative urine or serum pregnancy test for women of childbearing potential
- A second eligibility review will always be provided by a Head and Neck Research Team associated for the New Haven Campus and a third review will be provided by the PI.
Who cannot join
- Prior erlotinib, gefitinib or lapatinib therapy or prior exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor or any prior panitumumab or investigational EGFR-directed monoclonal antibody. Cetuximab is permitted if used for locally advanced disease, as long as no disease progression within 6 months. Cetuximab use is not permitted for recurrent/metastatic disease
- Radiotherapy within 2 weeks prior to enrollment. Palliative radiation to target organs may be allowed up to 2 weeks prior to enrollment, as long as there are other target lesions that can be monitored for response to study treatment.
- Known hypersensitivity to afatinib or its excipients
- Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control prior to study entry, for the duration of study participation and for at least 4 weeks after treatment has ended.
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
- Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug.
Show all 12Show fewer
- Concomitant malignancies at other sites that are being actively treated with systemic therapy
- Requiring treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation.
- Clinically significant interstitial lung disease.
- Known history of untreated viral hepatitis or HIV.
- Patients with parenchymal brain metastases are not eligible, unless they have completed local therapy
- Leptomeningeal carcinomatosis
Trial locations and contacts
1 site in 1 country.
United States1 site
Yale Cancer Center
New Haven, Connecticut, 06520-8028
About this study
Official title: Single-Arm Phase II Trial of Dual Inhibition of EGFR With Afatinib and Cetuximab With Correlative Studies in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck
This is a single arm Phase II study for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with an immune checkpoint inhibitor. The primary objective is to evaluate the efficacy of the combination of cetuximab and afatinib.
Read the detailed description
This study will be a multicenter, single-arm, open-label Phase II trial. Patients with advanced squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with immune checkpoint inhibitor therapy or both, will be eligible for participation on the study. After a baseline evaluation and biopsy (where feasible), they will be treated with weekly/bi-weekly intravenous cetuximab and daily oral afatinib. Biopsy will be repeated where feasible after 4 weeks (window of +1 week) on therapy and again at disease progression or end of treatment.
Treatment will continue until disease progression or development of Grade 3 or higher drug related toxicities that fail to resolve to Grade 2 despite appropriate supportive care.
- Being tested
- cetuximab, afatinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cetuximabDrug
Also called Erbitux
30-60 minutes after the recommended pre-medications, cetuximab will be administered intravenously at a dose of 400mg/m2 on cycle 1, day 1 of treatment (loading dose) and at a dose of 250mg/m2 every 7 days (+/- 1 day) thereafter. Alternatively, patients can be treated at a dose of 500mg/m2 every 14 days (+/- 2 days).
afatinibDrug
Also called GIOTRIF or GILOTRIF
Patients will take a single oral dose of afatinib each day at a dose of 30 mg. Afatinib dose will not be escalated beyond the 30 mg daily oral dose; dose reductions of afatinib can occur to manage treatment related adverse events.
| Study group | Role | What they receive |
|---|---|---|
| All subjects | Experimental | Advanced squamous cell carcinoma of the head and neck region, having previously been treated on a platinum based regimen or with an immune checkpoint inhibitor. Subjects will receive Afatinib dose 30 mg per day and weekly/bi-weekly intravenous cetuximab. Receives: Drug: cetuximab; Drug: afatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Shrinkage
Objective Response Rate (Complete Response + Partial Response), defined by tumor shrinkage (mm), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RECIST v1.1 Response Categories are as follows: Complete Response (CR) - all pathological lymph nodes must be < 10 mm in short axis; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) - The cancer has neither clearly improved nor worsened. Progressive Disease (PD) - at least a 20% increase in the sum of diameters of target lesions AND an absolute increase of ≥ 5 mm.
Measured: Disease progression or end of treatment (up to 2 years)
Secondary outcomes (4)
Progression-free Survival in Months
We will use Kaplan-Meier survival analysis to estimate the median PFS in the cohort. Data are presented by P16 status. The outcome measure title was updated to present the data in months, as analyzed, instead of weeks as originally registered.
Measured: 1 year follow-up
Overall Survival in Months
Measured by a monthly phone calls. We will use Kaplan-Meier survival analysis to estimate the median and OS in the cohort.
Measured: 1 year follow-up
Duration of Response in Weeks
Presented is the time from treatment onset until best response.
Measured: Up to 6 years
Toxicity Assessed With National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Presented are a count of those that experienced at least 1 adverse event. Adverse event details are presented in the Adverse Events module.
Measured: Up to 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2016 (estimated)
- Study start24 Mar 2017
- Primary completion18 Jan 2025
- Study completion18 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Squamous Cell Cancers of the Head and NeckStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Comprehensive Cancer Network, Boehringer Ingelheim
- Responsible party
- Sponsor
- Investigators
- Aarti Bhatia, MD, MPH, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02979977
- Sponsor's protocol ID
- 1608018260
- Status last verified
- Dec 2025
- First submitted
- 29 Nov 2016
- Last updated
- 4 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-Arm Phase II Trial of Dual Inhibition of EGFR With Afatinib and Cetuximab With Correlative Studies in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck
- ClinicalTrials.gov ID
- NCT02979977
- Acronym / sponsor ID
- 1608018260
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Comprehensive Cancer Network, Boehringer Ingelheim
- Study start
- 24 Mar 2017 (actual)
- Primary completion
- 18 Jan 2025 (actual)
- Study completion
- 18 Jan 2026 (actual)
- First posted
- 2 Dec 2016 (estimated)
- Results
- Posted 4 Feb 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single arm Phase II study for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with an immune checkpoint inhibitor. The primary objective is to evaluate the efficacy of the combination of cetuximab and afatinib.
Detailed description
This study will be a multicenter, single-arm, open-label Phase II trial. Patients with advanced squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with immune checkpoint inhibitor therapy or both, will be eligible for participation on the study. After a baseline evaluation and biopsy (where feasible), they will be treated with weekly/bi-weekly intravenous cetuximab and daily oral afatinib. Biopsy will be repeated where feasible after 4 weeks (window of +1 week) on therapy and again at disease progression or end of treatment.
Treatment will continue until disease progression or development of Grade 3 or higher drug related toxicities that fail to resolve to Grade 2 despite appropriate supportive care.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All subjects | Experimental | Drug: cetuximab, Drug: afatinibAdvanced squamous cell carcinoma of the head and neck region, having previously been treated on a platinum based regimen or with an immune checkpoint inhibitor. Subjects will receive Afatinib dose 30 mg per day and weekly/bi-weekly intravenous cetuximab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically confirmed squamous cell carcinoma of the head and neck that is metastatic, recurrent or locally advanced and not treatable with curative intent.
- Previous treatment with a platinum-based regimen or immune checkpoint inhibitor or both.2-week washout period prior to treatment start will be required.
- Patients who have experienced progression of disease within 6 months following completion of a platinum-based chemoradiation in the definitive or adjuvant setting will be permitted.
- Prior cetuximab permitted if it was given as part of multi-modality therapy for initial treatment of locally advanced disease.
- Measurable disease based on RECIST v 1.1. Baseline measurements and evaluations must be obtained within 4 weeks of enrollment. Disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy.
Key exclusion criteria (12 listed)
- Prior erlotinib, gefitinib or lapatinib therapy or prior exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor or any prior panitumumab or investigational EGFR-directed monoclonal antibody. Cetuximab is permitted if used for locally advanced disease, as long as no disease progression within 6 months. Cetuximab use is not permitted for recurrent/metastatic disease
- Radiotherapy within 2 weeks prior to enrollment. Palliative radiation to target organs may be allowed up to 2 weeks prior to enrollment, as long as there are other target lesions that can be monitored for response to study treatment.
- Known hypersensitivity to afatinib or its excipients
- Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control prior to study entry, for the duration of study participation and for at least 4 weeks after treatment has ended.
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cetuximabAlso: Erbitux30-60 minutes after the recommended pre-medications, cetuximab will be administered intravenously at a dose of 400mg/m2 on cycle 1, day 1 of treatment (loading dose) and at a dose of 250mg/m2 every 7 days (+/- 1 day) thereafter. Alternatively, patients can be treated at a dose of 500mg/m2 every 14 days (+/- 2 days). | Drug | All subjects |
| afatinibAlso: GIOTRIF or GILOTRIFPatients will take a single oral dose of afatinib each day at a dose of 30 mg. Afatinib dose will not be escalated beyond the 30 mg daily oral dose; dose reductions of afatinib can occur to manage treatment related adverse events. | Drug | All subjects |
Primary outcome
Tumor Shrinkage
Time frame: Disease progression or end of treatment (up to 2 years)
Objective Response Rate (Complete Response + Partial Response), defined by tumor shrinkage (mm), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RECIST v1.1 Response Categories are as follows: Complete Response (CR) - all pathological lymph nodes must be < 10 mm in short axis; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) - The cancer has neither clearly improved nor worsened. Progressive Disease (PD) - at least a 20% increase in the sum of diameters of target lesions AND an absolute increase of ≥ 5 mm.
4 secondary outcomes
Progression-free Survival in Months
Time frame: 1 year follow-up
Overall Survival in Months
Time frame: 1 year follow-up
Duration of Response in Weeks
Time frame: Up to 6 years
Toxicity Assessed With National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
Time frame: Up to 2.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Squamous Cell Cancers of the Head and Neck
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
RecruitingObservational study
Head and Neck Carcinoma Clinical Research Platform for Molecular and Blood-based Biomarkers, Treatment and Outcome
Squamous Cell Carcinoma of the Oral Cavity, Squamous Cell Carcinoma of the Oropharynx
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aarti Bhatia, MD, MPH principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cetuximab and afatinib in people with Squamous Cell Cancers of the Head and Neck, run by Yale University at 1 site 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 16 inclusion and 12 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 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 Feb 2026). 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?
Tumor Shrinkage (time frame: Disease progression or end of treatment (up to 2 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Feb 2026.