This phase II trial studies the side effects and best dose of ipilimumab, nivolumab, and radiation therapy and how well they work in treating patients with advanced human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma. Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, 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 to kill tumor cells and shrink tumors. Giving ipilimumab, nivolumab, and radiation therapy may work better in treating patients with HPV positive oropharyngeal squamous cell carcinoma.
PRIMARY OBJECTIVES: I. To evaluate the safety, tolerability and feasibility of ipilimumab and nivolumab when administered concurrently with reduced-field radiotherapy (intensity-modulated radiation therapy \[IMRT\]). II. To evaluate the clinical complete response rate to ipilimumab, nivolumab and IMRT with reduced field at six months as indicated by fluorodeoxyglucose - positron emission tomography/computed tomography (FDG-PET/CT) post completion of radiation therapy (RT). III. To evaluate the 2-year progression-free survival (PFS) rate of subjects with low-intermediate volume, local-regionally advanced, human papilloma virus (HPV)-positive squamous cell carcinoma of the head and neck (SCCHN) treated with ipilimumab, nivolumab and reduced-field IMRT. SECONDARY OBJECTIVES: I. To evaluate overall response rate to six weeks of induction immunotherapy (IO). II. To evaluate the frequency of pharyngeal dysphasia as measured by Dynamic Imaging (Dynamic Imaging Grade of Swallowing Toxicity \[DIGEST\]) grade on modified barium swallow (MBS) and patient-reported symptoms (MD Anderson Dysphagia Inventory \[MDADI\]) at 6 month, 1 and 2 years after radiotherapy (\[IMRT\]. III. To measure acute and chronic toxicities per Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (CTCAE PRO). IV. To measure acute toxicity profiles at the end of radiation therapy and IO and at 6 months. V. To measure late toxicity profiles at 1 and 2 years. VI. To determine local and regional control at 6 and 12 months. VII. To determine patterns of failure (local-regional relapse vs. distant) at 1 and 2 years. VIII. To determine overall survival (OS) at 1 and 2 years. CORRELATIVE OBJECTIVES: I. To evaluate associations between total mutational load, interferon (INF) gamma score, T cell clonality at diagnosis with clinical response to induction, combination CTLA-4 PD-1 checkpoint blockade. II. To evaluate changes in the tumor immune microenvironment (CD8 + INF gamma score, T cell clonality, in tumor biopsy specimens pre and post induction immunotherapy (IO). III. To evaluate dynamic changes in and clearance of oral HPV and cell-free deoxyribonucleic acid (cfDNA) viral load during therapy and to investigate associations with PFS and OS. EXPLORATORY OBJECTIVES: I. To evaluate changes in peripheral blood lymphocyte phenotypes and serum cytokine profiles before and after induction IO. II. To evaluate changes in the T cell receptor repertoire in tumor-infiltrating lymphocyte (TIL) and the peripheral blood in tumor biopsy specimens pre and post induction IO. III. To determine the negative and positive predictive values (NPV and PPV) of FDG-PET/CT 12-14 weeks after end of RT for 1 year and 2 year PFS and OS. OUTLINE: Patients receive nivolumab intravenously (IV) over 30 minutes on days 1, 15, and 29 and ipilimumab IV over 30 minutes on day 1. Treatment repeats every for 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning on day 1 of cycle 2, patients also undergo IMRT 5 days a week (Monday-Friday) for 6 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 2 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Undergo IMRT
Given IV
Given IV
Ancillary studies
Ancillary studies
M D Anderson Cancer Center
Houston, Texas, United States
Radiographic (RECIST) Response
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter with an absolute increase of at least 5 mm or the appearance of new lesions
Time frame: 6 months post completion of radiation therapy (approximately 9 months post start of treatment)
Pathologic Response -- Percent Viable Tumor Change
Pathologic response refers to the evaluation of how much a tumor has shrunk after treatment by the pathologist on trial examining tissue samples under a microscope. Tissue samples from baseline and at follow up were evaluated for tumor response. Percent viable tumor change is calculated using viable tumor data collected at the biopsy to the biopsy at the end of Cycle 1 of treatment.
Time frame: From first registration on trial (baseline biopsy) to post Cycle 1 of IO (6 weeks after start of treatment)
Toxicity (Number of Adverse Events)
Adverse events (AEs) are categorized as follows: Treatment-Emergent Adverse Events (TEAEs), which refer to any AEs that arise or worsen in severity after the initiation of treatment with the study product; and Treatment-Related Adverse Events (TRAEs), defined as TEAEs that are considered possibly, probably, or definitely related to the treatment. Adverse Events were graded 1 to 5 via CTAE 4.0 guidelines. All AEs, whether serious or non-serious, will be captured from the time of the first administration of the investigational agent until 30 days following the last dose of study drug or until the initiation of alternative anticancer therapy
Time frame: time of first drug administration to 30 days after last drug administration
Survival Analysis -- Progression Free Survival
Analyses of overall survival (OS) and progression-free survival (PFS) were performed. PFS was defined as from treatment initiation to progression or death, whichever occurred first, or last follow-up. The distribution was estimated by Kaplan-Meier method.
Time frame: 12 month post treatment follow up (15 months post treatment start), 18 month post treatment follow up (21 months post treatment start), 24 month post treatment follow up (27 months post treatment start)
Survival Analysis -- Overall Survival (Percentage of Participants Alive at 12 Months, 18 Months, and 24 Months)
Analyses of overall survival (OS) and progression-free survival (PFS) were performed. OS was defined as from treatment initiation to death or last follow-up time. The distribution was estimated by Kaplan-Meier method. No death was observed.
Time frame: 12 month post treatment follow up (15 months post treatment start), 18 month post treatment follow up (21 months post treatment start), 24 month post treatment follow up (27 months post treatment start)
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