Evaluating Unilateral Radiation Therapy with and without Cisplatin in Treating Patients with HPV 16+ Oropharyngeal Cancer

Status: active

This phase II trial evaluates whether patients with human papillomavirus 16-positive oropharyngeal cancer who receive radiation therapy to one side of the neck (unilateral) with or without cisplatin later develop cancer on the other (contralateral) side of the neck. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of cancer cells. The standard of care treatment for oropharyngeal cancer is radiation therapy to both sides of the neck (bilateral). Bilateral neck radiation delivers increased doses of radiation to healthy tissue, which can result in acute and late negative side effects. Patients who are considered to be at low risk for developing cancer on both sides of the neck may be able to be treated with unilateral rather than bilateral neck radiation, reducing negative side effects. The information gained from this trial will help determine whether patients who are treated with unilateral radiation therapy with and without cisplatin later develop contralateral oropharyngeal cancer.

Inclusion Criteria

Pathologically confirmed squamous cell carcinoma of the oropharynx
Patients to be treated with bilateral neck radiation per current guidelines must have either OR need to be present (see below): * Nodal status (based on staging manual, American Joint Committee on Cancer [AJCC] 8th edition [ed.]): N0 (provided the tumor is within 1cm of midline) N1 > 1 lymph nodes (on the same side of the neck as the primary cancer) or cN3 with no contralateral neck adenopathy * Tumor stage T1-2 that approaches within 1 cm but does not cross midline as appreciated radiographically and/or by the treating radiation oncologist or a head and neck surgeon
CT with contrast and/or MRI with contrast performed within 56 days prior to treatment initiation that does not demonstrate bilateral neck adenopathy. In the setting of medical contraindication to both CT and MRI contrast please contact the study principal investigator (PI)
PET/CT performed with 56 days prior to treatment that does not demonstrate bilateral neck adenopathy
Immunohistochemical staining for p16 that demonstrates moderate to severe staining in at least 70% of cells OR moderate to severe staining in < 70% of cells AND positive HPV DNA PCR and/or human papillomavirus (HPV) deoxyribonucleic acid (DNA) immunohistochemistry (ISH) and/or detectable HPV circulating tumor DNA (ctDNA) based upon investigator discretion regarding appropriateness
Patients must provide their smoking history prior to registration. Number of pack-years = (Frequency of smoking [number of cigarettes per day] x duration of cigarette smoking [years])/20
Patients must have clinically and/or radiographically evident disease that can be accurately measured in accordance with RECIST criteria version (v.) 1.1
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
Age >= 18 years
Adequate hematologic function within 28 days prior to treatment initiation
Adequate renal function within 28 days prior to treatment initiation
Adequate hepatic function within 28 days prior to treatment initiation

Exclusion Criteria

Tumors that cross midline, regardless of T stage
N2 adenopathy (bilateral neck adenopathy)
Gross total excision of the primary site in a diagnostic procedure prior to either imaging and/or physical examination by registering physician
p16-negative squamous cell carcinoma
Definitive clinical or radiologic evidence of metastatic disease or adenopathy below the clavicles
Prior systemic therapy for the study cancer
Prior head and neck cancer surgery that involved the neck (includes excisional biopsy)
Prior radiation therapy to the head and neck that would result in overlap of treated fields
History of allergic reaction attributed to Technetium-99m-tilmanocept used in lymphoscintigraphy
Uncontrolled intercurrent illness including, but not limited to, any other malignancy, other ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant or breast feeding

PRIMARY OBJECTIVE:

I. To evaluate the development of cancer on the contra-lateral side of the neck within 12 months of completion of radiation treatment.

SECONDARY OBJECTIVES:

I. To evaluate whether the omission of elective radiation to the contralateral neck decrease patient reported xerostomia at 6, 12, and 24 months to a mean score of 47.2 (from an expected 57.2) as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Head and Neck Module (QLQ H&N35).

II. To evaluate the functional swallowing change of patients treated with unilateral neck radiation as measured by a modified barium swallow for the period of one year after the end of radiotherapy.

III. To evaluate patient reported swallowing of patients treated with unilateral neck radiation as measured by the EORTC QLQ H&N 35 for the period of two years after the end of radiotherapy.

IV. To evaluate the development of cancer on the contra-lateral side of the neck within 24 months of completion of radiation treatment.

V. To evaluate the overall survival (OS) of head and neck cancer patients treated with unilateral neck radiation for the period of two years after the end of radiotherapy.

VI. To evaluate the disease free survival (DFS) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of head and neck cancer patients treated with unilateral neck radiation for the period of two years after the end of radiotherapy.

VII. To quantify the dosimetric degree of normal tissue avoidance of unilateral neck radiation when compared to bilateral neck radiation.

EXPLORATORY OBJECTIVES:

I. Characterize lymphatic drainage patterns of patients with lateralized head and neck cancer as determined by lymphoscintigraphy using summary statistics such as means, proportions, standard deviations, and 95% confidence intervals.

OUTLINE: All patients receive technetium Tc 99m-labeled tilmanocept via transoral injection and undergo single photon emission computed tomography (SPECT) or lymphoscintigraphy for treatment assignment. Patients with contralateral or bilateral lymphatic drainage are assigned to the conventional cohort. Patients determined to be at risk of developing contralateral neck cancer with > N1 multiple ipsilateral nodes of any size or single node > 3.0 cm nodal status are assigned to Cohort A. Patients determined to be at risk of developing contralateral neck cancer with N0 or N1 < 3.0 cm nodal status are assigned to Cohort B.

CONVENTIONAL COHORT: Patients undergo bilateral standard of care (SOC) neck radiation on study.

COHORT A: Patients undergo unilateral intensity-modulated radiation therapy (IMRT) for 35 fractions over 35 days and receive cisplatin intravenously (IV) or cetuximab IV or carboplatin IV in combination with paclitaxel IV or carboplatin IV alone once a week for 7 weeks on study. Patients also undergo contrast enhanced computed tomography (CT), contrast enhanced magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/CT at pre-treatment and follow up and undergo chest CT and modified barium swallow (MBS) at follow up. Patients may optionally undergo collection of blood samples and biopsy at pre-treatment and follow up.

COHORT B: Patients undergo unilateral IMRT for 35 fractions over 30 days on study. Patients also undergo contrast enhanced CT, contrast enhanced MRI, and/or PET/CT at pre-treatment and follow up and undergo chest CT and MBS at follow up. Patients may optionally undergo collection of blood samples and biopsy at pre-treatment and follow up.

Conventional cohort patients are followed as per standard of care. Cohort A and B patients are followed up at months 1 and 3 and then every 3 months for up to 24 months.

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Evaluating Unilateral Radiation Therapy with and without Cisplatin in Treating Patients with HPV 16+ Oropharyngeal Cancer

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United States

Pennsylvania

Philadelphia

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Evaluating Unilateral Radiation Therapy with and without Cisplatin in Treating Patients with HPV 16+ Oropharyngeal Cancer

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