Intensity-Modulated Radiation Therapy and Nivolumab in Treating Participants with Recurrent or Second Primary Head and Neck Squamous Cell Cancer
- 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
- 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
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
Emory University Hospital / Winship Cancer Institute
Nabil F. Saba
- Primary ID Winship4221-17
- Secondary IDs NCI-2018-00064, IRB00100923
- Clinicaltrials.gov ID NCT03521570