Recruiting
Phase 1

Immunotherapy & Surgery

Sponsor:

Ohio State University Comprehensive Cancer Center

Code:

NCT04754321

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

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

External Beam Radiation Therapy

Intraoperative Radiation Therapy

Pembrolizumab

Quality-of-Life Assessment

Salvage Surgery

Study Details

Brief 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). 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.

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

Study ID

NCT04754321

Start date

May 12, 2022

Status verified date

Jul, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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
  • 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

Exclusion Criteria:

  • 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
  • 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

Study Design

Enrollment

45 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A (pembrolizumab, salvage surgery, IORT)

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.

experimental: Arm B (pembrolizumab, EBRT, salvage surgery, IORT)

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.

experimental: Arm C (pembrolizumab, EBRT, salvage surgery, IORT)

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.

Interventions

External Beam Radiation Therapy

Undergo EBRT

Intraoperative Radiation Therapy

Undergo IORT

Pembrolizumab

Given IV

Quality-of-Life Assessment

Ancillary studies

Salvage Surgery

Undergo salvage surgery

Primary outcome measure

  • Incidence of adverse events [ Time Frame: Up to 100 days after last dose of study drug ]
  • Health related quality of life [ Time Frame: Up to 5 years ]

Central Contacts and Locations

Central contacts

The Ohio State University Comprehensive Cancer Center

800-293-5066OSUCCCClinicaltrials@osumc.edu

Locations

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Dukagjin M. Blakaj, MD, PhD

614-366-2729Dukagjin.Blakaj@osumc.edu

Principal Investigator:

Dukagjin M. Blakaj, MD, PhD

More Information

Sponsor

Ohio State University Comprehensive Cancer Center

Last update posted

Jul 24, 2026

Last verified

Jul, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Ohio State University Comprehensive Cancer Center on 2026-07-24.