Combining Immunotherapy Salvage Surgery & IORT Tx Persistent/Recurrent Head & Neck Cancer
HNSALV Trial: Combining Immunotherapy With Salvage Surgery and IORT for Treatment of Persistent/Recurrent Head and Neck Cancers
2 other identifiers
interventional
45
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started May 2022
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 9, 2021
CompletedFirst Posted
Study publicly available on registry
February 15, 2021
CompletedStudy Start
First participant enrolled
May 12, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
February 2, 2026
January 1, 2026
4.6 years
February 9, 2021
January 29, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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.
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.
Up to 5 years
Secondary Outcomes (5)
Objective-response rate (ORR)
Up to 5 years
Local control rate
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
Up to 5 years
Progression-free survival (PFS)
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
Up to 5 years
Study Arms (3)
Arm A (pembrolizumab, salvage surgery, IORT)
EXPERIMENTALPatients 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)
EXPERIMENTALPatients 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)
EXPERIMENTALPatients 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
Undergo IORT
Given IV
Undergo EBRT
Ancillary studies
Undergo salvage surgery
Eligibility Criteria
You may qualify if:
- 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)
- +8 more criteria
You may not qualify if:
- 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
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dukagjin M Blakaj, MD, PhD
Ohio State University Comprehensive Cancer Center
Central Study Contacts
The Ohio State University Comprehensive Cancer Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
February 9, 2021
First Posted
February 15, 2021
Study Start
May 12, 2022
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2026
Last Updated
February 2, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share