Head and Neck Carcinoma of Unknown PrimaryPhase 1NCT04754321
Combining Immunotherapy Salvage Surgery & IORT Tx Persistent/Recurrent Head & Neck Cancer
A Phase 1 study testing External Beam Radiation Therapy, Intraoperative Radiation Therapy and Pembrolizumab in people with Head and Neck Carcinoma of Unknown Primary and Locally Recurrent Head and Neck Squamous Cell Carcinoma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.
Trial summary
This phase I trial is to find out the possible side effects of pembrolizumab and radiation therapy before and during surgery in treating patients with head and neck squamous cell cancer that remains despite treatment (persistent) or has come back (recurrent). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Carcinoma of Unknown Primary, Locally Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma
- What is being tested?
- External Beam Radiation Therapy, Intraoperative Radiation Therapy and Pembrolizumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 12 May 2022to 31 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Pathologically confirmed either persistent and/ or locoregionally recurrent HNSCC of oral cavity, pharynx, larynx, unknown primary head and neck (H\&N) squamous cell carcinoma
- Resectable disease as determined by the surgeon and team
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2
- At least 18 years of age
- Adequate hematologic, renal, and hepatic function
- Must have at least 2 week washout period from prior therapy
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- Willingness and ability to provide informed consent
- Negative pregnancy test for females of reproductive potential
- Patients who have undergone therapy for their cancer, such as surgery and/or chemotherapy and/or radiotherapy and recurred
- Disease measurable by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria.
- Prior definitive and palliative chemotherapy will be allowed
- Prior radiation therapy will be allowed
- Tumor tissue from resected site of disease must be provided for biomarker analyses, in addition to urine and blood sample as scheduled per protocol
- White blood cell (WBC) >= 2000/uL (obtained within 14 days of randomization)
- Neutrophils >= 1500/uL (obtained within 14 days of randomization)
- Platelets >= 100 x10^3/uL (obtained within 14 days of randomization)
- Hemoglobin > 9.0 g/dL (obtained within 14 days of randomization)
- Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance (CrCl) >= 40 mL/min (Cockcroft and Gault or Wright formula may be used according to local practice) (obtained within 14 days of randomization)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x institutional ULN
- Total Bilirubin =< 1.5 x institutional ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
- Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for four months after the last dose of pembrolizumab.
- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG])
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men who are sexually active with WOCBP will be instructed to adhere to contraception for a period of four months after the last dose of investigational product
Who cannot join
- Requirement of immunosuppressive therapy within 14 days of randomization
- Salivary gland carcinomas, lip carcinoma, adenocarcinoma of the skin
- Prior use of immune checkpoint blockade agent
- History of human immunodeficiency virus (HIV), hepatitis B, C: Participants who test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection, those who test positive for human immunodeficiency virus (HIV) or have known acquired immunodeficiency syndrome (AIDS)
- Unresectable disease, as determined by the surgeon and team
- Subjects with history of grade 3 toxicity with prior immunotherapy
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- Patients with distant metastases
- Subjects with active autoimmune disease
- Breastfeeding women
- Additional prior malignancy within the previous 3 years (treated or untreated, except for skin carcinomas treated with excision alone and carcinoma in situ of the cervix)
- Palliative radiotherapy less than 14 days prior to first dose of study drug
- Any history of hypersensitivity to any of the trial medications
- Poorly controlled or serious medical or psychiatric illness likely to interfere with participation and/or compliance in this clinical trial
- Prisoners or subjects who are involuntarily incarcerated
- Patients not available for follow-up/future contact as defined in the ICF
- Note: Patients on this protocol are not excluded from participation in other clinical trials
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
The Ohio State University Comprehensive Cancer Center contact
United States1 site, 1 recruiting
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Dukagjin M. Blakaj, MD, PhD, 614-366-2729, Dukagjin.Blakaj@osumc.edu
Dukagjin M. Blakaj, MD, PhD
About this study
Official title: HNSALV Trial: Combining Immunotherapy With Salvage Surgery and IORT for Treatment of Persistent/Recurrent Head and Neck Cancers
This phase I trial is to find out the possible side effects of pembrolizumab and radiation therapy before and during surgery in treating patients with head and neck squamous cell cancer that remains despite treatment (persistent) or has come back (recurrent). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays or protons to kill tumor cells and shrink tumors. Giving pembrolizumab and radiation therapy before and during surgery may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate the potential toxicity of immunotherapy and preoperative radiation combined with intra-operative radiation in patients with recurrent or persistent head and neck squamous cell carcinoma (HNSCC).
SECONDARY OBJECTIVES:
- To evaluate the clinical efficacy, measured as a locoregional control rate (LCR) and progression-free survival (PFS), of immunotherapy and preoperative radiation combined with intra-operative radiation in patients with recurrent or persistent HNSCC.
II. To evaluate the pre-operative radiation dose effect (0 Gy, 2 Gy X 2, 8 Gy X 2) on anti-tumor immune response in the setting of immunotherapy in patients with recurrent or persistent HNSCC.
III. To evaluate the radiation dose effect (0 Gy, 2 Gy X 2, 8 Gy X 2) on the expression of the deoxyribonucleic acid (DNA) exonuclease Trex1.
IV. To compare the overall survival (OS) of pembrolizumab and pre and post-operative external beam radiation therapy (EBRT) plus intraoperative radiation therapy (IORT) in subjects with recurrent or persistent HNSCC.
- To assess the overall safety and tolerability of pre-operative pembrolizumab and pre-operative EBRT and IORT plus post-operative pembrolizumab versus pre-operative pembrolizumab plus IORT and post-operative pembrolizumab in subjects with with recurrent or persistent HNSCC.
VI. To evaluate whether PD-L1 expression is a predictive biomarker for LCR and PFS.
VII. To evaluate whether TNF-alpha expression is a predictive biomarker for LCR and PFS.
VIII. To evaluate whether NFkappaB expression is a predictive biomarker for LCR and PFS.
IX. To evaluate whether tumor mutational burden is predictive of immunotherapy response.
- To evaluate the Health Related Quality of Life (HRQoL) as assessed by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-HN35.
EXPLORATORY OBJECTIVES:
- To evaluate associations between gene expression status of tumor samples and clinical efficacy (LRC, PFS and overall survival [OS]).
II. To evaluate whether mutational burden is a predictive biomarker for LCR and PFS.
III. To explore potential biomarkers associated with clinical efficacy (LRC, PFS, and OS) by analyzing circulating tumor DNA quantitative load with polymerase chain reaction (PCR), chemokines/cytokines and immune cells (e.g. CD8+ T cells, regulatory T cells [Tregs], myeloid derived suppressor cells [MDSCs]) with FACS in blood, tumor tissue and correlating those with clinical outcomes.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM A: Patients receive pembrolizumab intravenously (IV) on day 1 of week 1, and undergo salvage surgery during week 4. Beginning week 8, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo intraoperative radiation therapy (IORT) for 1 fraction during week 9. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab.
ARM B: Patients receive pembrolizumab IV on day 1 of week 1, and undergo low dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab.
ARM C: Patients receive pembrolizumab IV on day 1 of week 1, and undergo high dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab.
After completion of study treatment, patients are followed up at 90 and 180 days, then every 90 weeks for 24 months, and then every 6 months up to year 5.
- Conditions
- Head and Neck Carcinoma of Unknown Primary, Locally Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Oral Cavity Squamous Cell Carcinoma, Recurrent Pharyngeal Squamous Cell Carcinoma, Resectable Head and Neck Squamous Cell Carcinoma
- Being tested
- External Beam Radiation Therapy, Intraoperative Radiation Therapy, Pembrolizumab, Quality-of-Life Assessment, Salvage Surgery
- 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.
External Beam Radiation TherapyRadiation
Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy
Undergo EBRT
Intraoperative Radiation TherapyRadiation
Also called Intraoperative Radiotherapy, IORT, radiotherapy, intraoperative
Undergo IORT
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Salvage SurgeryProcedure or surgery
Also called Rescue Surgery, Salvage Resection, Salvage Surgical Resection, Surgical Salvage
Undergo salvage surgery
| Study group | Role | What they receive |
|---|---|---|
| Arm A (pembrolizumab, salvage surgery, IORT) | Experimental | Patients receive pembrolizumab IV on day 1 of week 1, and undergo salvage surgery during week 4. Beginning week 8, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 9. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab. Receives: Radiation: Intraoperative Radiation Therapy; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Procedure: Salvage Surgery |
| Arm B (pembrolizumab, EBRT, salvage surgery, IORT) | Experimental | Patients receive pembrolizumab IV on day 1 of week 1, and undergo low dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab. Receives: Radiation: External Beam Radiation Therapy; Radiation: Intraoperative Radiation Therapy; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Procedure: Salvage Surgery |
| Arm C (pembrolizumab, EBRT, salvage surgery, IORT) | Experimental | Patients receive pembrolizumab IV on day 1 of week 1, and undergo high dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab. Receives: Radiation: External Beam Radiation Therapy; Radiation: Intraoperative Radiation Therapy; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Procedure: Salvage Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. Summarized by treatment group. All on-study adverse events (AEs), treatment-related AEs, serious (S)AEs, and treatment-related SAEs will be tabulated using worst grade per NCI CTCAE version 4.0 criteria by system organ class and preferred term. On-study lab parameters including hematology, chemistry, liver function, and renal function will also be summarized using worst grade NCI CTCAE v 4.0 criteria. Toxicity will be measured as the rate of grade 3 and 4 adverse events and will be calculated through using the exact binomial distribution method with a 2- sided 95% confidence interval.
Measured: Up to 100 days after last dose of study drug
Health related quality of life
Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30. Analysis will be performed in all randomized participants who have an assessment at baseline and at least one follow-up assessment using linear mixed model for repeated measures to model the changes overtime for each arm.
Measured: Up to 5 years
Secondary outcomes (5)
Objective-response rate (ORR)
ORR including complete response rate, partial response rate, and stable disease rate will be calculated using the exact binomial distribution method with a 2- sided 95% confidence interval among patients who obtain a least one dose of study drug.
Measured: Up to 5 years
Local control rate
Analyses will be conducted using Kaplan-Meier method for each arm. The hazard ratio and corresponding two-sided 95% CI will be estimated using a Cox proportional hazards model, with treatment group as a single covariate.
Measured: From the first day of therapy to the occurrence of a local and/or regional recurrence (whichever comes first), and death from any cause other than distant metastasis, assessed up to 24 months
Overall survival
Analyses will be conducted using Kaplan-Meier method for each arm. The hazard ratio and corresponding two-sided 95% CI will be estimated using a Cox proportional hazards model, with treatment group as a single covariate.
Measured: Up to 5 years
Progression-free survival (PFS)
Analyses will be conducted using Kaplan-Meier method for each arm. The PFS medians with 95% confidence intervals (CIs), and PFS at 6, 12, and 24 months with 95% CIs will be estimated a two-sided log-rank test. The hazard ratio and corresponding two-sided 95% CI will be estimated using a Cox proportional hazards model, with treatment group as a single covariate, stratified by the above factors.
Measured: From the first day of the therapy to the appearance of local or regional recurrence, distant metastases, secondary primary cancer or death from any cause, assessed up to 24 months
PD-L1 expression
A Cox proportional hazards model will be used to test the interaction between PD-L1 expression (positive vs negative) and treatment arm.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2021
- Study start12 May 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (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 Carcinoma of Unknown PrimaryStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ohio State University Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dukagjin Blakaj, Ohio State University Comprehensive Cancer Center
- Investigators
- Dukagjin M Blakaj, MD, PhD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04754321
- Sponsor's protocol ID
- OSU-20297
- Other IDs
- NCI-2021-00036
- Status last verified
- Jul 2026
- First submitted
- 9 Feb 2021
- Last updated
- 24 Jul 2026
- Results posted
- No
- 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 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HNSALV Trial: Combining Immunotherapy With Salvage Surgery and IORT for Treatment of Persistent/Recurrent Head and Neck Cancers
- ClinicalTrials.gov ID
- NCT04754321
- Acronym / sponsor ID
- OSU-20297
- Conditions
- Head and Neck Carcinoma of Unknown Primary, Locally Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Oral Cavity Squamous Cell Carcinoma, Recurrent Pharyngeal Squamous Cell Carcinoma, Resectable Head and Neck Squamous Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Ohio State University Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 12 May 2022 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 15 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial is to find out the possible side effects of pembrolizumab and radiation therapy before and during surgery in treating patients with head and neck squamous cell cancer that remains despite treatment (persistent) or has come back (recurrent). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays or protons to kill tumor cells and shrink tumors. Giving pembrolizumab and radiation therapy before and during surgery may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVE:
- To evaluate the potential toxicity of immunotherapy and preoperative radiation combined with intra-operative radiation in patients with recurrent or persistent head and neck squamous cell carcinoma (HNSCC).
SECONDARY OBJECTIVES:
- To evaluate the clinical efficacy, measured as a locoregional control rate (LCR) and progression-free survival (PFS), of immunotherapy and preoperative radiation combined with intra-operative radiation in patients with recurrent or persistent HNSCC.
II. To evaluate the pre-operative radiation dose effect (0 Gy, 2 Gy X 2, 8 Gy X 2) on anti-tumor immune response in the setting of immunotherapy in patients with recurrent or persistent HNSCC.
III. To evaluate the radiation dose effect (0 Gy, 2 Gy X 2, 8 Gy X 2) on the expression of the deoxyribonucleic acid (DNA) exonuclease Trex1.
IV. To compare the overall survival (OS) of pembrolizumab and pre and post-operative external beam radiation therapy (EBRT) plus intraoperative radiation therapy (IORT) in subjects with recurrent or persistent HNSCC.
- To assess the overall safety and tolerability of pre-operative pembrolizumab and pre-operative EBRT and IORT plus post-operative pembrolizumab versus pre-operative pembrolizumab plus IORT and post-operative pembrolizumab in subjects with with recurrent or persistent HNSCC.
VI. To evaluate whether PD-L1 expression is a predictive biomarker for LCR and PFS.
VII. To evaluate whether TNF-alpha expression is a predictive biomarker for LCR and PFS.
VIII. To evaluate whether NFkappaB expression is a predictive biomarker for LCR and PFS.
IX. To evaluate whether tumor mutational burden is predictive of immunotherapy response.
- To evaluate the Health Related Quality of Life (HRQoL) as assessed by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-HN35.
EXPLORATORY OBJECTIVES:
- To evaluate associations between gene expression status of tumor samples and clinical efficacy (LRC, PFS and overall survival [OS]).
II. To evaluate whether mutational burden is a predictive biomarker for LCR and PFS.
III. To explore potential biomarkers associated with clinical efficacy (LRC, PFS, and OS) by analyzing circulating tumor DNA quantitative load with polymerase chain reaction (PCR), chemokines/cytokines and immune cells (e.g. CD8+ T cells, regulatory T cells [Tregs], myeloid derived suppressor cells [MDSCs]) with FACS in blood, tumor tissue and correlating those with clinical outcomes.
OUTLINE: Patients are randomized to 1 of 3 arms.
ARM A: Patients receive pembrolizumab intravenously (IV) on day 1 of week 1, and undergo salvage surgery during week 4. Beginning week 8, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo intraoperative radiation therapy (IORT) for 1 fraction during week 9. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab.
ARM B: Patients receive pembrolizumab IV on day 1 of week 1, and undergo low dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab.
ARM C: Patients receive pembrolizumab IV on day 1 of week 1, and undergo high dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab.
After completion of study treatment, patients are followed up at 90 and 180 days, then every 90 weeks for 24 months, and then every 6 months up to year 5.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A (pembrolizumab, salvage surgery, IORT) | Experimental | Radiation: Intraoperative Radiation Therapy, Biological: Pembrolizumab, Other: Quality-of-Life Assessment, Procedure: Salvage SurgeryPatients receive pembrolizumab IV on day 1 of week 1, and undergo salvage surgery during week 4. Beginning week 8, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 9. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab. |
| Arm B (pembrolizumab, EBRT, salvage surgery, IORT) | Experimental | Radiation: External Beam Radiation Therapy, Radiation: Intraoperative Radiation Therapy, Biological: Pembrolizumab, Other: Quality-of-Life Assessment, Procedure: Salvage SurgeryPatients receive pembrolizumab IV on day 1 of week 1, and undergo low dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab. |
| Arm C (pembrolizumab, EBRT, salvage surgery, IORT) | Experimental | Radiation: External Beam Radiation Therapy, Radiation: Intraoperative Radiation Therapy, Biological: Pembrolizumab, Other: Quality-of-Life Assessment, Procedure: Salvage SurgeryPatients receive pembrolizumab IV on day 1 of week 1, and undergo high dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Pathologically confirmed either persistent and/ or locoregionally recurrent HNSCC of oral cavity, pharynx, larynx, unknown primary head and neck (H\&N) squamous cell carcinoma
- Resectable disease as determined by the surgeon and team
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2
- At least 18 years of age
- Adequate hematologic, renal, and hepatic function
Key exclusion criteria (16 listed)
- Requirement of immunosuppressive therapy within 14 days of randomization
- Salivary gland carcinomas, lip carcinoma, adenocarcinoma of the skin
- Prior use of immune checkpoint blockade agent
- History of human immunodeficiency virus (HIV), hepatitis B, C: Participants who test positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection, those who test positive for human immunodeficiency virus (HIV) or have known acquired immunodeficiency syndrome (AIDS)
- Unresectable disease, as determined by the surgeon and team
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 |
|---|---|---|
| External Beam Radiation TherapyAlso: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam RadiotherapyUndergo EBRT | Radiation | Arm B (pembrolizumab, EBRT, salvage surgery, IORT), Arm C (pembrolizumab, EBRT, salvage surgery, IORT) |
| Intraoperative Radiation TherapyAlso: Intraoperative Radiotherapy, IORT, radiotherapy, intraoperativeUndergo IORT | Radiation | Arm A (pembrolizumab, salvage surgery, IORT), Arm B (pembrolizumab, EBRT, salvage surgery, IORT), Arm C (pembrolizumab, EBRT, salvage surgery, IORT) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Arm A (pembrolizumab, salvage surgery, IORT), Arm B (pembrolizumab, EBRT, salvage surgery, IORT), Arm C (pembrolizumab, EBRT, salvage surgery, IORT) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Arm A (pembrolizumab, salvage surgery, IORT), Arm B (pembrolizumab, EBRT, salvage surgery, IORT), Arm C (pembrolizumab, EBRT, salvage surgery, IORT) |
| Salvage SurgeryAlso: Rescue Surgery, Salvage Resection, Salvage Surgical Resection, Surgical SalvageUndergo salvage surgery | Procedure or surgery | Arm A (pembrolizumab, salvage surgery, IORT), Arm B (pembrolizumab, EBRT, salvage surgery, IORT), Arm C (pembrolizumab, EBRT, salvage surgery, IORT) |
Primary outcome
Incidence of adverse events
Time frame: Up to 100 days after last dose of study drug
Evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. Summarized by treatment group. All on-study adverse events (AEs), treatment-related AEs, serious (S)AEs, and treatment-related SAEs will be tabulated using worst grade per NCI CTCAE version 4.0 criteria by system organ class and preferred term. On-study lab parameters including hematology, chemistry, liver function, and renal function will also be summarized using worst grade NCI CTCAE v 4.0 criteria. Toxicity will be measured as the rate of grade 3 and 4 adverse events and will be calculated through using the exact binomial distribution method with a 2- sided 95% confidence interval.
Health related quality of life
Time frame: Up to 5 years
Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30. Analysis will be performed in all randomized participants who have an assessment at baseline and at least one follow-up assessment using linear mixed model for repeated measures to model the changes overtime for each arm.
5 secondary outcomes
Objective-response rate (ORR)
Time frame: Up to 5 years
Local control rate
Time frame: From the first day of therapy to the occurrence of a local and/or regional recurrence (whichever comes first), and death from any cause other than distant metastasis, assessed up to 24 months
Overall survival
Time frame: Up to 5 years
Progression-free survival (PFS)
Time frame: From the first day of the therapy to the appearance of local or regional recurrence, distant metastases, secondary primary cancer or death from any cause, assessed up to 24 months
PD-L1 expression
Time frame: Up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Thermal Ablation and Spine Stereotactic Radiosurgery in Treating Patients With Spine Metastases at Risk for Compressing the Spinal Cord
Malignant Digestive System Neoplasm, Metastatic Head and Neck Carcinoma
RecruitingObservational study
Blood Tests and Questionnaires in Studying Adherence to Preventative Swallowing Exercises in Participants With Metastatic Head and Neck Cancer
Carcinoma of Unknown Primary, Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
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.
The Ohio State University Comprehensive Cancer Center contact
Dukagjin M Blakaj, MD, PhD principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing External Beam Radiation Therapy, Intraoperative Radiation Therapy and Pembrolizumab in people with Head and Neck Carcinoma of Unknown Primary and Locally Recurrent Head and Neck Squamous Cell Carcinoma, run by Ohio State University Comprehensive Cancer Center 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 23 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 24 Jul 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact The Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCClinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 100 days after last dose of study drug). 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?
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 24 Jul 2026; AzTrials last refreshed its copy on 31 Oct 2026.