Head and Neck CancerPhase 1/2NCT03247712
Neoadjuvant Immunoradiotherapy in Head & Neck Cancer
A Phase 1/2 study testing Nivolumab, Surgical Resection and Radiation (5 days) in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, run by Providence Health & Services at 1 site in United States.
Trial summary
The purpose of this study is to test the safety of neoadjuvant immunoradiotherapy as a safe means of down-staging Head and Neck Squamous Cell Carcinoma (HNSCC) prior to surgical resection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
- What is being tested?
- Nivolumab, Surgical Resection and Radiation (5 days)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2018to Dec 2026
- Phase
- Phase 1/2
- 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
- Patients with squamous cell carcinoma of the head and neck region, (including mucosal,cutaneous, or nodal) who are planned for surgical resection and in the opinion of the investigator are able to safely undergo neoadjuvant anti-PD-1 and radiation. In addition, the following are eligible (but will not contribute toward total accrual): non-surgical cases that are planned for palliative RT or that refuse or are unfit for definitive concurrent chemotherapy.
- HPV status as determined by p16 immunostain
- Cohort 3: HPV-positive patients only
- Cohort 4: HPV-negative patients only
- Age 18 years or above with ability to give informed consent, comply with the protocol, and sign a study-specific consent document. Patients with history of psychiatric illness must be judged by the investigator as able to understand the investigational nature and risks associated with the therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status deemed suitable by investigator for study requirements.
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- Laboratory values (most recent), must be within 6 weeks of week 0 on study:
- WBC ≥ 2000/uL, ANC ≥ 1000/uL
- Hgb > 8g/dL (patients may be transfused to reach this level)
- Platelets > 50,000 cells/mm3
- Creatinine ≤ 3 x ULN
- AST/ALT ≤ 5 x ULN for subjects without liver metastasis; or ≤ 8 x ULN for subjects with liver metastasis, [per investigator brochure]
- Total bilirubin ≤ 3 x ULN, (except subjects with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
- Negative pregnancy test (bHCG urine or serum, women of childbearing potential only)
- Women of child-bearing potential (WOCBP) must agree to follow adequate contraceptive practices to avoid pregnancy for the duration of treatment with nivolumab plus 5 half-lives of nivolumab (75 days) plus 30 days (duration of ovulatory cycle) for a total of 105 days post-treatment completion.
- Males who are sexually active with WOCBP must agree to follow adequate contraceptive practices to avoid pregnancy for the duration of treatment with study drug (s) plus 5 half lives of the study drug (75 days) plus 90 days (duration of sperm turnover) for a total of 165 days post-treatment completion.
Who cannot join
- Any clinical factors such as bleeding, active infection, or psychiatric factors that in the judgment of the investigator would preclude safe participation and compliance with study procedures.
- HNSCC for which radiation is not indicated during normal treatment course.
- Need for chronic maintenance with oral steroids ≥20mg daily prednisone equivalent; inhaled, topical or non-absorbed steroids are acceptable.
- History of or current active autoimmune disease, [e.g. including but not limited to inflammatory bowel diseases [IBD], rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome)], which in the judgment of the investigator poses an active and significant morbidity risk. Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary. Patient and investigator may opt to accept risk of autoimmune disease flare, based on shared-decision making with consideration of risk/benefit.
Trial locations and contacts
1 site in 1 country.
United States1 site
Providence Portland Medical Center
Portland, Oregon, 97213
About this study
Official title: Neoadjuvant Immunoradiotherapy: Head & Neck Cancer (NIRT-HNC)
The purpose of this study is to test the safety of neoadjuvant immunoradiotherapy as a safe means of down-staging Head and Neck Squamous Cell Carcinoma (HNSCC) prior to surgical resection.
Read the detailed description
This clinical trial uses nivolumab and radiotherapy prior to definitive surgical resection of tumors in patients with Head and Neck Squamous Cell Carcinoma (OHNSCC) with the primary objective of determining the safety and feasibility of preoperative immunoradiotherapy. In addition, tumor tissue, microbiome samples, and peripheral blood will be obtained for exploratory immunologic end points including measurements of tumor infiltrating immune cell populations based on flow cytometry and immunohistochemistry as well as circulating immunological parameters. This is the first study to evaluate the safety and efficacy of neoadjuvant radiation + PD-1 blockade in patients with HNSCC.
Estimated duration of 20 weeks: neoadjuvant immunoradiotherapy +/- surgery, followed by 6 doses of nivolumab 480mg IV q4wks +/- risk-adapted adjuvant therapy, per standard of care.
Phase I safety lead-in study (n = 6) evaluating the safety of neoadjuvant immunoradiotherapy in HNSCC, followed by phase II efficacy study (n = 28, total) to assess rate of down-staging after neoadjuvant immunoradiotherapy using Simon's two-stage design (futility assessment at n = 12).
The phase 1 portion of this study will require 6 patients and is therefore expected to complete in 6 months. Although non-surgical patients are eligible to enroll, they will not be counted toward accrual for either the primary safety endpoint, (as by definition, unplanned delay of surgery cannot exist); nor the secondary efficacy endpoint, as potential for surgical staging is absent.
So long as 2 or fewer surgical delays are observed (primary safety endpoint), the phase 2 portion of study will proceed (secondary efficacy endpoint). Patients will be followed for disease free and overall survival at 5 years.
Eligible patients may be enrolled unless a rate of unplanned surgical delay attributed to immunoradiotherapy is found to exceed 33% after enrollment of the first 6 patients. We estimate 10 to 20 patients per year will be enrolled.
- Being tested
- Nivolumab, Surgical Resection, Radiation (5 days), Radiation (3 days)
- Keywords
- HNSCC, radiation, surgery, phase 1, immunotherapy, nivolumab, antibodies
- Medical subject headings
- Head and Neck Neoplasms, 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.
NivolumabDrug
Also called Opdivo
Nivolumab 240mg IV q2wks or 480mg IV q4wks
Surgical ResectionProcedure or surgery
Surgical Resection of Tumor
Radiation (5 days)Radiation
8Gy x 5 (Mon-Fri) GTV+3mm
Radiation (3 days)Radiation
8Gy x 3 (Monday, Wednesday, Friday) GTV+3mm
| Study group | Role | What they receive |
|---|---|---|
| Treatment Cohort 1 | Experimental | Nivolumab administration (3 doses) and radiation (5 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses). Receives: Drug: Nivolumab; Procedure: Surgical Resection; Radiation: Radiation (5 days) |
| Treatment Cohort 2 | Experimental | Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses). Receives: Drug: Nivolumab; Procedure: Surgical Resection; Radiation: Radiation (3 days) |
| Treatment Cohort 3 | Experimental | Radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses). Receives: Drug: Nivolumab; Procedure: Surgical Resection; Radiation: Radiation (3 days) |
| Treatment Cohort 4 | Experimental | Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses). Receives: Drug: Nivolumab; Procedure: Surgical Resection; Radiation: Radiation (3 days) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with an Unplanned Delay to Surgery [Safety and Tolerability of Neoadjuvant Treatment]
Safety endpoint: Number of patients with an Unplanned Delay to Surgery defined as any change to scheduled surgery date considered to be at least possibly related to neoadjuvant treatment.
Measured: 6 weeks
Secondary outcomes (1)
Number of patients with decrease in tumor size or number of lymph nodes involved [Efficacy of Neoadjuvant Treatment]
Efficacy endpoint: Number of patients with decrease in tumor size of greater than 10% or decrease in the number of lymph nodes involved by 10% by week 6.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2017
- Study start15 Jan 2018
- Primary completion13 Feb 2020
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Head and Neck CancerStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Providence Health & Services
- Sponsor type
- University, hospital or other
- Collaborators
- Providence Cancer Center, Earle A. Chiles Research Institute
- Responsible party
- Sponsor
- Investigators
- Rom Leidner, MD, Principal investigator, Providence Health and Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03247712
- Sponsor's protocol ID
- NIRT-HNC
- Status last verified
- Jul 2026
- First submitted
- 8 Aug 2017
- Last updated
- 23 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, Patel AA, Cheng AC, Watters AL, Bifulco C, Morris G, Rushforth L, Nemeth S, Urba WJ, Gough M, Bell RB. Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma. J Immunother Cancer. 2021 May;9(5):e002485. doi: 10.1136/jitc-2021-002485.
PubMed 33963014
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Immunoradiotherapy: Head & Neck Cancer (NIRT-HNC)
- ClinicalTrials.gov ID
- NCT03247712
- Acronym / sponsor ID
- NIRT-HNC
- Keywords
- HNSCC, radiation, surgery, phase 1, immunotherapy, nivolumab, antibodies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Providence Health & ServicesUniversity, hospital or other
- Collaborators
- Providence Cancer Center, Earle A. Chiles Research Institute
- Study start
- 15 Jan 2018 (actual)
- Primary completion
- 13 Feb 2020 (actual)
- Study completion
- Dec 2026 (estimated)
- First posted
- 14 Aug 2017 (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.
The purpose of this study is to test the safety of neoadjuvant immunoradiotherapy as a safe means of down-staging Head and Neck Squamous Cell Carcinoma (HNSCC) prior to surgical resection.
Detailed description
This clinical trial uses nivolumab and radiotherapy prior to definitive surgical resection of tumors in patients with Head and Neck Squamous Cell Carcinoma (OHNSCC) with the primary objective of determining the safety and feasibility of preoperative immunoradiotherapy. In addition, tumor tissue, microbiome samples, and peripheral blood will be obtained for exploratory immunologic end points including measurements of tumor infiltrating immune cell populations based on flow cytometry and immunohistochemistry as well as circulating immunological parameters. This is the first study to evaluate the safety and efficacy of neoadjuvant radiation + PD-1 blockade in patients with HNSCC.
Estimated duration of 20 weeks: neoadjuvant immunoradiotherapy +/- surgery, followed by 6 doses of nivolumab 480mg IV q4wks +/- risk-adapted adjuvant therapy, per standard of care.
Phase I safety lead-in study (n = 6) evaluating the safety of neoadjuvant immunoradiotherapy in HNSCC, followed by phase II efficacy study (n = 28, total) to assess rate of down-staging after neoadjuvant immunoradiotherapy using Simon's two-stage design (futility assessment at n = 12).
The phase 1 portion of this study will require 6 patients and is therefore expected to complete in 6 months. Although non-surgical patients are eligible to enroll, they will not be counted toward accrual for either the primary safety endpoint, (as by definition, unplanned delay of surgery cannot exist); nor the secondary efficacy endpoint, as potential for surgical staging is absent.
So long as 2 or fewer surgical delays are observed (primary safety endpoint), the phase 2 portion of study will proceed (secondary efficacy endpoint). Patients will be followed for disease free and overall survival at 5 years.
Eligible patients may be enrolled unless a rate of unplanned surgical delay attributed to immunoradiotherapy is found to exceed 33% after enrollment of the first 6 patients. We estimate 10 to 20 patients per year will be enrolled.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment Cohort 1 | Experimental | Drug: Nivolumab, Procedure: Surgical Resection, Radiation: Radiation (5 days)Nivolumab administration (3 doses) and radiation (5 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses). |
| Treatment Cohort 2 | Experimental | Drug: Nivolumab, Procedure: Surgical Resection, Radiation: Radiation (3 days)Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses). |
| Treatment Cohort 3 | Experimental | Drug: Nivolumab, Procedure: Surgical Resection, Radiation: Radiation (3 days)Radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses). |
| Treatment Cohort 4 | Experimental | Drug: Nivolumab, Procedure: Surgical Resection, Radiation: Radiation (3 days)Nivolumab administration (3 doses) and radiation (3 days) therapy prior to restaging and surgical resection followed by additional administration of nivolumab (3 doses). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients with squamous cell carcinoma of the head and neck region, (including mucosal,cutaneous, or nodal) who are planned for surgical resection and in the opinion of the investigator are able to safely undergo neoadjuvant anti-PD-1 and radiation. In addition, the following are eligible (but will not contribute toward total accrual): non-surgical cases that are planned for palliative RT or that refuse or are unfit for definitive concurrent chemotherapy.
- HPV status as determined by p16 immunostain
- Cohort 3: HPV-positive patients only
- Cohort 4: HPV-negative patients only
- Age 18 years or above with ability to give informed consent, comply with the protocol, and sign a study-specific consent document. Patients with history of psychiatric illness must be judged by the investigator as able to understand the investigational nature and risks associated with the therapy.
Key exclusion criteria (4 listed)
- Any clinical factors such as bleeding, active infection, or psychiatric factors that in the judgment of the investigator would preclude safe participation and compliance with study procedures.
- HNSCC for which radiation is not indicated during normal treatment course.
- Need for chronic maintenance with oral steroids ≥20mg daily prednisone equivalent; inhaled, topical or non-absorbed steroids are acceptable.
- History of or current active autoimmune disease, [e.g. including but not limited to inflammatory bowel diseases [IBD], rheumatoid arthritis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome)], which in the judgment of the investigator poses an active and significant morbidity risk. Vitiligo and adequately controlled endocrine deficiencies such as hypothyroidism are not exclusionary. Patient and investigator may opt to accept risk of autoimmune disease flare, based on shared-decision making with consideration of risk/benefit.
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 |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab 240mg IV q2wks or 480mg IV q4wks | Drug | Treatment Cohort 1, Treatment Cohort 2, Treatment Cohort 3, Treatment Cohort 4 |
| Surgical ResectionSurgical Resection of Tumor | Procedure or surgery | Treatment Cohort 1, Treatment Cohort 2, Treatment Cohort 3, Treatment Cohort 4 |
| Radiation (5 days)8Gy x 5 (Mon-Fri) GTV+3mm | Radiation | Treatment Cohort 1 |
| Radiation (3 days)8Gy x 3 (Monday, Wednesday, Friday) GTV+3mm | Radiation | Treatment Cohort 2, Treatment Cohort 3, Treatment Cohort 4 |
Primary outcome
Number of patients with an Unplanned Delay to Surgery [Safety and Tolerability of Neoadjuvant Treatment]
Time frame: 6 weeks
Safety endpoint: Number of patients with an Unplanned Delay to Surgery defined as any change to scheduled surgery date considered to be at least possibly related to neoadjuvant treatment.
1 secondary outcome
Number of patients with decrease in tumor size or number of lymph nodes involved [Efficacy of Neoadjuvant Treatment]
Time frame: 6 weeks
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 23 Jul 2026.
- Derived from this study: PubMed 33963014Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, Patel AA, Cheng AC, Watters AL, Bifulco C, Morris G, Rushforth L, Nemeth S, Urba WJ, Gough M, Bell RB. Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma. J Immunother Cancer. 2021 May;9(5):e002485. doi: 10.1136/jitc-2021-002485.
- Providence Cancer CenterLink provided by the sponsor.
- 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.
Rom Leidner, MD principal investigator
Providence Health and Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Nivolumab, Surgical Resection and Radiation (5 days) in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, run by Providence Health & Services 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 16 inclusion and 4 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: under way, not looking for participants, as of the sponsor's last update on 23 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 combined 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.
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?
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?
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?
Number of patients with an Unplanned Delay to Surgery [Safety and Tolerability of Neoadjuvant Treatment] (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03247712, which also lists 1 linked publication.
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 23 Jul 2026.