Radiation Therapy and Docetaxel in Treating Patients With HPV-Related Oropharyngeal Cancer

Study Overview
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Brief Summary
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This phase II trial studies how well radiation therapy and docetaxel work in treating patients with human papillomavirus (HPV)-related oropharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving radiation therapy with docetaxel my kill more tumor cells.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the cumulative incidence of local/regional failure at 2 years after study registration. SECONDARY OBJECTIVES: I. To characterize the rate of acute grade 3 or higher functional mucosal adverse events (up to 1 month post-radiation therapy [XRT]) associated with adjuvant docetaxel + hyperfractionated radiotherapy (key secondary endpoint). II. To assess changes in overall survival, disease-free survival, distant failure rates, and quality of life (QOL) associated with adjuvant docetaxel and hyperfractionated radiation. III. To characterize other acute adverse events (up to 1 month post-XRT) and late grade 3 or higher non-hematologic adverse events (up to 2 years post-XRT) associated with adjuvant docetaxel + hyperfractionated radiotherapy. TERTIARY OBJECTIVES: I. To determine the genetic alterations of oropharynx tumor specimens and the detection rate of corresponding cell-free deoxyribonucleic acid (cfDNA) in the pre-surgical, post-surgical, and post-radiation blood of oropharynx cancer patients. OUTLINE: Patients receive docetaxel intravenously (IV) over 1 hour on days 1 and 8 and undergo hyperfractionated intensity-modulated radiation therapy (IMRT) twice daily (BID) 5 days a week on days 1-12 for a total of 20 fractions. After completion of study treatment, patients are followed up at 14 days, 1 month, every 3 months for 2 years, every 6 months for 1 year and then annually for 2 years.

Official Title
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Phase II Evaluation of Adjuvant Hyperfractionated Radiation and Docetaxel for HPV Associated Oropharynx Cancer

Conditions
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Human Papillomavirus Infection, Stage I Oropharyngeal Squamous Cell Carcinoma, Stage II Oropharyngeal Squamous Cell Carcinoma, Stage III Oropharyngeal Squamous Cell Carcinoma, Stage IVA Oropharyngeal Squamous Cell Carcinoma, Stage IVB Oropharyngeal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Docetaxel
* Radiation: Hyperfractionation
* Radiation: Intensity-Modulated Radiation Therapy
* Other: Laboratory Biomarker Analysis
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PRE-REGISTRATION Provide written informed consent Submission of research blood draw to be stored until after surgical resection of the primary tumor and confirmation of human papilloma virus (HPV) positivity (Mayo Clinic Rochester patients only) Patients with oropharynx carcinoma with a smoking history of ˂ 10 pack-year or equivalent 10 year history of tobacco product use and no recent history (within last 5 years) of tobacco use REGISTRATION Histological confirmation of HPV+ squamous cell carcinoma of the oropharynx; HPV positivity will be defined as positive staining for p16 on immunohistochemistry (IHC) Gross total surgical resection with curative intent of the primary tumor and at least unilateral neck dissection within 7 weeks of registration Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 Smoking history < 10 pack years or equivalent 10 year history of tobacco product use Absence of distant metastases on standard diagnostic work-up =< 10 weeks prior to registration; (chest computed tomography [CT], chest x-ray [CXR], positron emission tomography [PET]/CT, etc.) Must have one of the following risk factors: Lymph node > 3 cm 2 or more positive lymph nodes Perineural invasion Lymphovascular space invasion T3 or microscopic T4a primary disease Lymph node extracapsular extension Absolute neutrophil count (ANC) >= 1500/mm^3 Platelet count >= 100,000/mm^3 Hemoglobin >= 9.0 g/dL Direct bilirubin within upper limit of normal (ULN) Creatinine =< ULN x 1.5 Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only Ability to complete questionnaire(s) by themselves or with assistance Provide informed written consent Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study) Exclusion Criteria: Any significant tobacco history within the past five years Any of the following: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive Uncontrolled intercurrent illness including, but not limited to, 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 Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm Other active malignancy =< 5 years prior to registration; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix; NOTE: if there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer History of myocardial infarction =< 180 days prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias Prior history of radiation therapy to the affected site History of connective tissue disorders such as rheumatoid arthritis, lupus, or Sjogren's disease Presence of any of the following risk factors after surgery: Any positive surgical margin Adenopathy below the clavicles Prior systemic chemotherapy for the study cancer; NOTE: prior chemotherapy for a different cancer is allowable History of allergic reaction to docetaxel Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) Use of strong or moderate inhibitors is prohibited =< 7 days prior to registration Receiving any medications or substances that are inducers of CYP3A4 Use of inducers is prohibited =< 12 days prior to registration

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (docetaxel, hyperfractionated IMRT)<br>Patients receive docetaxel IV over 1 hour on days 1 and 8 and undergo hyperfractionated IMRT BID 5 days a week on days 1-12 for a total of 20 fractions. | Drug: Docetaxel<br>* Given IV<br>* Other names: Taxotere Injection Concentrate;Radiation: Hyperfractionation<br>* Undergo hyperfractionated IMRT<br>* Other names: superfractionated radiation therapy;Radiation: Intensity-Modulated Radiation Therapy<br>* Undergo hyperfractionated IMRT<br>* Other names: Intensity-Modulated Radiotherapy;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year Loco-regional Tumor Control (LRC) Rate | The 2-year loco-regional tumor control (LRC) rate (percentage) is defined as the percentage of patients with no local/regional recurrence or death 2 years after study registration. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Grade 3 or Higher Mucositis Oral | The overall percentage of patients experiencing grade 3 or higher mucositis oral graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 are reported below. | 4 months post-hyperfractionated radiation therapy | 
| 2-year Overall Survival (OS) Rate | The distribution of OS will be estimated using the method of Kaplan-Meier. | 2 years | 
| 2-year Progression-free Survival (PFS) | The distribution of PFS will be estimated using the method of Kaplan-Meier. | From registration to the first of either disease recurrence or death, assessed up to 2 years | 
| 2-year Distant Metastasis-free Survival Rate | The 2-year Distant metastasis-free survival rate (percentage) is defined as the percentage of patients with no distant recurrence or death 2 years after study registration. | 2 years | 
| Change From Mean Baseline Score to Mean Score at 12 Months Post-RT in Swallow Function as Measured by the Pharyngeal Total Modified Barium Swallow Impairment Profile. | The swallow evaluation consists of a modified barium swallow study(MBS), Functional Oral Intake Scale(FOIS), and Performance Status Scale Head & Neck(PSS-HN).The 17 swallow questions are rated using a 0 to 5 point scale, with 0 meaning no impairment and 5 max impairment. 6 questions produce a total oral score; scores from 10 questions produce a total pharyngeal score; 1 question produces an esophageal score.The PAS is a validated 8-point scale that ranks the depth of the bolus entry into the airway.A score of 1 indicates no airway entrance;score of 6+ indicate bolus passage past the vocal folds (aspiration).FOIS ranges from 1(nothing by mouth) to 7(total oral diet with no restrictions).PSS-H&N has 3 components:eating in public(0=always eat alone to 100=no restriction), understandability of speech(0=never understandable, score 100=always understandable), and normalcy of diet(score 0=tube fed to 100=full diet).These scores are summed and normalized to a 0 to 100 scale where 100 is best. | 12 months | 
| Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (Version 4) | The FACT-H&N is a multidimensional, self-report QOL instrument specifically designed for use with head and neck cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, in addition to 12 site specific items to assess for head and neck related symptoms. Each item is rated on a 0 to 4 type scale where 4 is favorable and 0 unfavorable, and then combined to produce subscale scores for each domain, as well as a global QOL score- with possible score range from 0 to 156. Higher scores represent better QOL. | 1 year | 
| European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35) | QOL was measured by the European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35) at baseline and at 1-year post-treatment. Each question scores 0-4, with 0 being favorable and 4 being unfavorable. The average total score at baseline and average total score at 12 months post-RT is reported. The max total score possible is 140(Unfavorable) and the minimum total score possible is 0(Favorable). An increase in score indicates a greater quality of life A paired t-test compares the scores at these two timepoints. | 1 year post-treatment | 
| EuroQol Five-dimensional Instrument (EQ-5D-3L) | QOL was measured by the three-level version of the EuroQol five-dimensional instrument (EQ-5D-3L) at baseline and 1-year post-treatment. This consisted of 5 questions, each score 0 to 3 points with 3 being unfavorable and 0 being favorable. The total possible score per patient per time point is 15 and a minimum score of 0(favorable). The change in average total score at baseline and 12 months post-RT is reported. A paired t-test compares the scores at these two time points. A higher score indicates greater impairment. | 1 year post-treatment |