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Intensity-Modulated Radiation Therapy and Nivolumab in Treating Participants with Recurrent or Second Primary Head and Neck Squamous Cell Cancer

Trial Status: Active

This phase II trial studies how well intensity-modulated radiotherapy and nivolumab work together in treating participants with head and neck squamous cell cancer that has come back (recurrent). Intensity-modulation radiation therapy uses varying intensities of radiation beams to kill cancer cells and shrink tumors, thereby reducing the damage to nearby healthy tissue. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving intensity-modulated radiation therapy and nivolumab may work better at treating head and neck squamous cell cancer.

Inclusion Criteria

  • All patients included in this trial must be candidates for re-irradiation with IMRT
  • Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field
  • Life expectancy of greater than 6 months
  • Patients cannot have distant metastases and have to be candidates for curative re-irradiation
  • Patients with salivary gland tumors are excluded (patients with nasopharynx carcinoma [CA] or sinonasal cancers can participate)
  • Patients with unresectable disease are eligible
  • Patients who undergo surgical resection will be allowed regardless of human papilloma virus (HPV) status provided they have one of the following criteria: * Positive margins on pathology * Evidence of extracapsular spread on nodal pathology * Gross residual disease on postoperative or simulation imaging * N2/3 disease * T3/4 disease * Multifocal perineural invasion and/or lymphovascular space invasion
  • The majority of the anticipated target volume (> 50%) must have been previously treated to >= 40 Gy; prior radiation therapy (RT) must have been completed > 6 months prior to initiation of IMRT reirradiation; if previous RT records are unavailable, investigators can estimate the dose to previously treated tissues based on completion notes or other treatment history
  • An Eastern Cooperative Oncology Group (ECOG) performance score 0-2
  • Granulocytes > 1500/mm^3
  • Platelets > 100,000/mm^3
  • Bilirubin < 1.5 mg/dl
  • Creatinine < 1.5 mg/dl
  • No other concurrent invasive malignancies treated for the past year (localized prostate cancer or early stage skin cancer are not exclusion criteria)
  • Patients with carotid artery involvement or encasement will be allowed provided they have no symptoms related to carotid involvement
  • No prior exposure to immunotherapy agents
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Any known factors that would pose a contraindication to receiving nivolumab
  • Recursive partitioning analysis (RPA) class III patients defined as those expected to begin reirradiation within 2 years of first course of radiation therapy AND are percutaneous endoscopic gastrostomy [PEG] dependent or have a tracheostomy (patients who have undergone total laryngectomy are not excluded)
  • Patients with metastases
  • Prior treatment with a PD-1/PD-L1 inhibitor
  • Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment
  • Patients with primary salivary gland cancers are excluded
  • Patients who have had chemotherapy or biological therapy within 4 weeks of registration
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease requiring systemic steroids, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients who are pregnant or breast-feeding
  • Patients with known active human immunodeficiency virus (HIV), hepatitis (hep) B, or hep C infection
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease


Emory University Hospital / Winship Cancer Institute
Status: ACTIVE
Contact: Nabil F. Saba
Phone: 404-778-3995
Emory University Hospital Midtown
Status: ACTIVE
Contact: Nabil F. Saba
Phone: 404-778-3995


Cleveland Clinic Foundation
Status: ACTIVE
Contact: Shlomo Asher Koyfman
Phone: 216-444-7552


Medical College of Wisconsin
Status: ACTIVE
Contact: Stuart J. Wong
Phone: 866-680-0505


I. To assess the 1-year progression-free survival (PFS) for patients with recurrent or second primary head and neck squamous cancer treated with intensity-modulated radiation therapy (IMRT) re-irradiation with concurrent and adjuvant nivolumab.


I. Evaluate the 1-year (yr) overall survival (OS) of patients treated with re-irradiation and nivolumab.

II. Evaluate patient quality of life (QOL).

III. Evaluate patterns of failure including local, regional and distant failure rates at 1 yr.

IV. Identify and estimate the incidence rate of acute and late toxicities associated with combined re-irradiation and concurrent and adjuvant nivolumab.


I. To identify potential biomarkers related to clinical benefit to concurrent and adjuvant nivolumab and re-irradiation in patients with recurrent or second primary (RSP) head and neck squamous cell carcinoma (HNSCC).


Participants receive nivolumab intravenously (IV) over 30-60 minutes on weeks -2, 0, 2, 4, and 6 and undergo IMRT once daily (QD) beginning on week 0 for up to 6-6.5 weeks. Beginning week 10, participants receive nivolumab IV over 30-60 minutes every 4 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up for 2 years from the start of radiation therapy.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Emory University Hospital / Winship Cancer Institute

Principal Investigator
Nabil F. Saba

  • Primary ID Winship4221-17
  • Secondary IDs NCI-2018-00064, IRB00100923
  • ID NCT03521570