Head and Neck Squamous Cell CarcinomaPhase 2NCT03383094
Chemoradiation vs Immunotherapy and Radiation for Head and Neck Cancer
A Phase 2 study testing Pembrolizumab, Radiation therapy and Cisplatin in people with Head and Neck Squamous Cell Carcinoma and Cancer, run by Loren Mell, MD at 6 sites in United States.
Trial summary
The purpose of this study is to compare any good or bad effects of using pembrolizumab (an experimental drug) and radiation therapy (RT), compared to using cisplatin chemotherapy and radiation therapy (RT) in the treatment of patients with head and neck squamous cell carcinoma (HNSCC). 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, Cancer, Cancer of Head and Neck
- What is being tested?
- Pembrolizumab, Radiation therapy and Cisplatin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 6 sitesUnited States
- Study dates
- 15 Mar 2018to 31 Dec 2027
- Phase
- Phase 2
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
- p16-positive squamous cell carcinoma of the pharynx, larynx or oral cavity
- High-Intermediate Risk Disease, defined as:
- T1-T3 N2 M0 or T3 N1 M0 or any stage III (T4 or N3) p16+ squamous cell carcinoma of the oropharynx (AJCC 8th edition staging system)
- T1-2 N1-3 M0 or T3-4 N0-3 M0 (stage III-IVB) p16+ squamous cell carcinoma of the hypopharynx or larynx
- T1-2 N2-3 M0 or T3-4 N0-3 M0 (stage III-IVB) p16+ squamous cell carcinoma of the nasopharynx
- Inoperable T4 N0-3 M0 (stage IVA-IVB) p16+ squamous cell carcinoma of the oral cavity
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- Measurable disease based on RECIST 1.1
- Adequate hematologic function within 28 days prior to registration
- Adequate renal and hepatic function
- Female subject of childbearing potential should have a negative pregnancy test
- Female subjects of childbearing potential must agree to use an adequate method of contraception for the course of the study
- Male subjects must agree to use an adequate method of contraception for the course of the study
Who cannot join
- Prior malignancy within the past 3 years (except non-melanomatous skin cancer and early stage treated prostate cancer);
- Prior head and neck radiation, chemotherapy, or immunotherapy;
- Prior oncologic (radical) surgery to the primary site;
- Documented evidence of distant metastases;
- Severe, active co-morbidity defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
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- Transmural myocardial infarction within the last 6 months;
- Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration;
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration;
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol.
- Any medical or psychiatric illness, which, in the opinion of the principal investigator, would compromise the patient's ability to tolerate this treatment;
- Psychiatric/social situations that would limit compliance with study requirements
- Hypersensitivity to pembrolizumab or any of its excipients.
- 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.
- Known history of, or any evidence of active, non-infectious pneumonitis.
- Active infection requiring systemic therapy.
- 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.
- Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- 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 planned start of study therapy.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37203
Washington University School of Medicine, Siteman Cancer Center
St Louis, Missouri, 63110
H. Lee Moffitt Cancer Center & Research Facility
Tampa, Florida, 33612
University of Arizona Cancer Center
Tucson, Arizona, 85719
About this study
Official title: Phase II Randomized Trial of Radiotherapy With Concurrent and Adjuvant Pembrolizumab (Keytruda®) Versus Concurrent Chemotherapy in Patients With Advanced/Intermediate-Risk p16+ Head and Neck Squamous Cell Carcinoma (KEYCHAIN)
The purpose of this study is to compare any good or bad effects of using pembrolizumab (an experimental drug) and radiation therapy (RT), compared to using cisplatin chemotherapy and radiation therapy (RT) in the treatment of patients with head and neck squamous cell carcinoma (HNSCC).
Read the detailed description
This study is a prospective, multi-institutional, open-label, randomized phase II trial that will evaluate the efficacy of concurrent and adjuvant pembrolizumab with radiation therapy (RT) versus RT plus cisplatin in intermediate/high-riskp16-positive locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The primary endpoint is progression-free survival (PFS).
- Conditions
- Head and Neck Squamous Cell Carcinoma, Cancer, Cancer of Head and Neck, Cancer, Advanced, Cancer, Metastatic, Tumor
- Being tested
- Pembrolizumab, Radiation therapy, Cisplatin
- Keywords
- cancer, Head and Neck, Pembrolizumab, Cisplatin, Radiotherapy, Head and Neck Squamous Cell Carcinoma, p16+, immunotherapy, pd-1, chemotherapy, T1, T2, T3, N2, M0, T4, N3, N1
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Neoplasms, Head and Neck Neoplasms, Neoplasm Metastasis, Recurrence, Mouth Neoplasms, Oropharyngeal Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Immunotherapy
Pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles
Radiation therapyRadiation
Also called Radiotherapy
70 Gy in 33-35 fractions
CisplatinDrug
Also called Chemotherapy
100 mg/m2 Weeks 1, 4, and 7.
| Study group | Role | What they receive |
|---|---|---|
| Control-radiotherapy/cisplatin | Active comparator | Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent cisplatin 100 mg/m2 every 3 weeks for 3 cycles (7 weeks) Receives: Radiation: Radiation therapy; Drug: Cisplatin |
| Experimental-Radiotherapy/pembrolizumab | Experimental | Intensity-modulated radiation therapy to 70 Gy in 33-35 fractions over 6.5 weeks plus concurrent and adjuvant pembrolizumab 200 mg IV infusion every 3 weeks x 20 cycles Receives: Drug: Pembrolizumab; Radiation: Radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival (PFS)
time from randomization to progression/relapse or death from any cause.
Measured: 3 years
Secondary outcomes (4)
overall survival
time from randomization to death from any cause
Measured: 3 years
Acute toxicity
Toxicities due to therapy occurring within 3 months of therapy completion based on CTCAE criteria using questionnaires
Measured: 3 months
Late toxicity
Toxicity due to therapy occurring greater than 3 months after completion of therapy based on CTCAE criteria using questionnaires
Measured: 3 years
Patterns of failure
Local and regional and distant recurrence of cancer and causes of death from competing events
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2017
- Study start15 Mar 2018
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck Squamous Cell CarcinomaStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 126 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loren Mell, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Loren Mell, MD, University of California, San Diego
- Investigators
- Loren Mell, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03383094
- Sponsor's protocol ID
- 170862
- Status last verified
- Oct 2025
- First submitted
- 18 Dec 2017
- Last updated
- 7 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No