Head and Neck Squamous Cell CarcinomaPhase 2NCT02892201
Pembrolizumab in HNSCC With Residual Disease After Radiation
A Phase 2 study testing Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Yale University at 2 sites in United States.
Trial summary
This is a phase II study for patients with squamous cell carcinoma of the head and neck who have residual disease following definitive therapy with radiation (with or without systemic therapy). Patients must be diagnosed with residual disease within 24 weeks of completion of radiation therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Sep 2016to Mar 2020
- 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
- Be willing and able to provide written informed consent/assent for the trial.
- Be => 18 years of age on day of signing informed consent.
- Biopsy proven residual disease.
- Be willing to provide tissue from a newly obtained core biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1 and following completion of RT/CRT.
- Have a performance status of 0 or 1 or 2 on the ECOG Performance Scale.
- Demonstrate adequate organ function. Labs value need to be assessed within 14 days of study treatment.
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- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- Patients must have a history of Stage I-IVB SCC of the head and neck arising from the oral cavity, oropharynx, nasopharynx, larynx, or hypopharynx and must have been treated with definitive intent radiation (with or without systemic therapy)
- Patients must be at least 6 weeks (42 days) and no more than 24 weeks (168 days) from completion of radiation with or without systemic therapy at the time of biopsy confirming residual disease. Patients must receive the first dose of study medication no more than 28 weeks following completion of radiation.
- Patients must have pathological evidence of persistent lymph node disease or persistent disease at the primary tumor site with viable tumor cells confirmed by a biopsy within 24 weeks of study treatment and no evidence of metastatic disease following primary radiation with or without systemic therapy confirmed by a CT scan within 4 weeks of study treatment. If a biopsy confirming residual disease has not been performed, this can be performed after obtaining consent during the screening procedures.
- Persistent lymph node disease with viable tumor cells will be determined by the histological determination of tumor viability.
- All persistent disease must have received at least 66 Gy in 1.8-2Gy fractions of radiotherapy to the area of residual disease (or a biologically equivalent dose given by the linear quadratic equation: biologically equivalent dose (BED) = nd (1 + d/( α/β), where n is the number of fractions, d dose per fraction and the α/β ratio for tumor is 10. Previous radiation records will be obtained to confirm adequate dosing.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving supraphysiologic doses of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. A physiologic dose of steroids is defined as up to 10mg of prednisone daily (or its equivalent).
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from acute, non-hematological adverse events due to agents administered more than 4 weeks earlier, unless otherwise approved by the Principal Investigator.
- Note: Subjects with ≤ Grade 2 neuropathy, any grade dysphagia, ≤ Grade 2 pain, ≤ Grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any grade xerostomia, and any grade dysgeusia, are an exception to this criterion and may qualify for the study. Also please note that the presence of a feeding tube to aid with nutrition does not disqualify patients from study.
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- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to the first protocol treatment or who has not recovered (i.e., ≤ Grade 1 or at baseline) from acute, non-hematological adverse events due to a previously administered agent, unless otherwise approved by the Principal Investigator.
- Note: Subjects with ≤ Grade 2 neuropathy, any grade dysphagia, ≤ Grade 2 pain, ≤ Grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any grade xerostomia, and any grade dysgeusia, are an exception to this criterion and may qualify for the study. Also please note that the presence of a feeding tube to aid with nutrition does not disqualify patients from study.
- Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has known history of non-infectious pneumonitis that required steroids, or current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of the first protocol treatment. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
- Any patient receiving adjuvant systemic therapy following the completion of radiation therapy is ineligible.
- Any patient with evidence of distant metastatic disease on a CT within 4 weeks of treatment is ineligible.
- Evidence of interstitial lung disease.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Texas Southwestern Medical Center (UTSW)
Dallas, Texas, 75390
Yale Cancer Center
New Haven, Connecticut, 06520
About this study
Official title: A Phase II Study of Pembrolizumab for Patients With Head and Neck Squamous Cell Carcinoma With Residual Disease Following Definitive Chemoradiation
This is a phase II study for patients with squamous cell carcinoma of the head and neck who have residual disease following definitive therapy with radiation (with or without systemic therapy). Patients must be diagnosed with residual disease within 24 weeks of completion of radiation therapy. Residual disease must be biopsy proven before the patient can consent to the trial, and can be either from lymph nodes in the neck, or from the primary tumor site. Prior to beginning study therapy patients are evaluated by an ENT to determine if they have disease amenable to surgical resection. Both resectable and unresectable patients will be eligible for participation in the study.
Read the detailed description
The primary objective is to determine the overall response to pembrolizumab for patients with residual disease following radiation with or without systemic therapy for squamous cell carcinoma of the head and neck.
Hypothesis: The use of pembrolizumab in patients with residual disease following radiation with or without systemic therapy will lead to an enhanced overall response rate due to treatment-related priming of the immune response.
When initially registered, the study used a follow up assessment of 12 weeks. However, the actual study aims for the primary and secondary outcomes were updated to 168 weeks. The primary completion date was also updated to reflect the primary outcome timeline.
Following results entry and QC review, the Overall Response Rate at 168 weeks secondary outcome, defined as a composite of 2 measures, was removed as it was reported in separate outcomes.
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Being tested
- Pembrolizumab
- 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.
PembrolizumabDrug
Also called Keytruda, MK-3475
a constant dose of 200 mg every three weeks, for four cycles.
| Study group | Role | What they receive |
|---|---|---|
| All subjects | Experimental | for patients with squamous cell carcinoma of the head and neck who have residual disease following definitive therapy with radiation
Pembrolizumab will be given at a constant dose of 200 mg every three weeks, for four cycles. Patients with resectable disease can then go on to surgery, and patients with unresectable disease can continue on pembrolizumab until progression or for up to 1 year. Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
To determine the overall response rate based on RECIST 1.1 to pembrolizumab for patients with residual disease following radiation with or without systemic therapy for squamous cell carcinoma of the head and neck. For lesions considered too small for measurement by RECIST 1.1 a modified response criteria will be used. RECIST categories used for the target lesion are complete response (CR), partial response (PR), stable disease (NR/SD), and progressive disease (PD). Upon entry of results, the time frame was corrected to 12 weeks (see attached protocol).
Measured: 12 weeks
Secondary outcomes (4)
Change in PD-L1 Expression
To determine changes in PD-L1 expression following irradiation, the Modified Proportion Score or MPS was used. MPS is a scale of 0-100 and it represents the overall % positive cells expressing PD-L1 where the greater the score, the more likely there will be a response to treatment. This outcome was updated/corrected at the time of results entry.
Measured: Up to 4 weeks
Median Progression Free Survival
To evaluate median progression free survival in days. Upon entry of results, the time frame was corrected to the full amount of time that participants were followed up with.
Measured: Up to 168 weeks
Overall Survival
To evaluate overall survival. Overall survival is presented as a count of those deceased and living at the end of the follow up period.
Measured: 168 weeks
Median Overall Survival
To evaluate overall survival, the median overall survival time is presented in days through the study and follow up periods.This outcome was reported at the time of results entry to compliment the count of participants in the Overall Survival outcome.
Measured: Up to 168 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2016 (estimated)
- Study start8 Sep 2016
- Primary completionFeb 2020
- Study completionMar 2020
Why it stopped: Low enrollment
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 Head and Neck Squamous Cell CarcinomaStudies 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
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Barbara Burtness, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02892201
- Sponsor's protocol ID
- 2000028047
- Other IDs
- 1602017275
- Status last verified
- Jul 2025
- First submitted
- 19 Aug 2016
- Last updated
- 29 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Pembrolizumab for Patients With Head and Neck Squamous Cell Carcinoma With Residual Disease Following Definitive Chemoradiation
- ClinicalTrials.gov ID
- NCT02892201
- Acronym / sponsor ID
- 2000028047
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low enrollment
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 8 Sep 2016 (actual)
- Primary completion
- Feb 2020 (actual)
- Study completion
- Mar 2020 (actual)
- First posted
- 8 Sep 2016 (estimated)
- Results
- Posted 18 Nov 2023
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 phase II study for patients with squamous cell carcinoma of the head and neck who have residual disease following definitive therapy with radiation (with or without systemic therapy). Patients must be diagnosed with residual disease within 24 weeks of completion of radiation therapy. Residual disease must be biopsy proven before the patient can consent to the trial, and can be either from lymph nodes in the neck, or from the primary tumor site. Prior to beginning study therapy patients are evaluated by an ENT to determine if they have disease amenable to surgical resection. Both resectable and unresectable patients will be eligible for participation in the study.
Detailed description
The primary objective is to determine the overall response to pembrolizumab for patients with residual disease following radiation with or without systemic therapy for squamous cell carcinoma of the head and neck.
Hypothesis: The use of pembrolizumab in patients with residual disease following radiation with or without systemic therapy will lead to an enhanced overall response rate due to treatment-related priming of the immune response.
When initially registered, the study used a follow up assessment of 12 weeks. However, the actual study aims for the primary and secondary outcomes were updated to 168 weeks. The primary completion date was also updated to reflect the primary outcome timeline.
Following results entry and QC review, the Overall Response Rate at 168 weeks secondary outcome, defined as a composite of 2 measures, was removed as it was reported in separate outcomes.
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: Pembrolizumabfor patients with squamous cell carcinoma of the head and neck who have residual disease following definitive therapy with radiation Pembrolizumab will be given at a constant dose of 200 mg every three weeks, for four cycles. Patients with resectable disease can then go on to surgery, and patients with unresectable disease can continue on pembrolizumab until progression or for up to 1 year. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Be willing and able to provide written informed consent/assent for the trial.
- Be => 18 years of age on day of signing informed consent.
- Biopsy proven residual disease.
- Be willing to provide tissue from a newly obtained core biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1 and following completion of RT/CRT.
- Have a performance status of 0 or 1 or 2 on the ECOG Performance Scale.
Key exclusion criteria (25 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving supraphysiologic doses of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. A physiologic dose of steroids is defined as up to 10mg of prednisone daily (or its equivalent).
- Has a known history of active TB (Bacillus Tuberculosis)
- Hypersensitivity to pembrolizumab or any of its excipients.
- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from acute, non-hematological adverse events due to agents administered more than 4 weeks earlier, unless otherwise approved by the Principal Investigator.
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 |
|---|---|---|
| PembrolizumabAlso: Keytruda, MK-3475a constant dose of 200 mg every three weeks, for four cycles. | Drug | All subjects |
Primary outcome
Overall Response Rate
Time frame: 12 weeks
To determine the overall response rate based on RECIST 1.1 to pembrolizumab for patients with residual disease following radiation with or without systemic therapy for squamous cell carcinoma of the head and neck. For lesions considered too small for measurement by RECIST 1.1 a modified response criteria will be used. RECIST categories used for the target lesion are complete response (CR), partial response (PR), stable disease (NR/SD), and progressive disease (PD). Upon entry of results, the time frame was corrected to 12 weeks (see attached protocol).
4 secondary outcomes
Change in PD-L1 Expression
Time frame: Up to 4 weeks
Median Progression Free Survival
Time frame: Up to 168 weeks
Overall Survival
Time frame: 168 weeks
Median Overall Survival
Time frame: Up to 168 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Barbara Burtness, MD principal investigator
Yale University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Head and Neck Squamous Cell Carcinoma, run by Yale 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 14 inclusion and 25 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: stopped early, as of the sponsor's last update on 29 Jul 2025. 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 18 Nov 2023). 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 (time frame: 12 weeks). 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 29 Jul 2025.