Phase II Evaluation of Adjuvant Hyperfractionated Radiation and Docetaxel for HPV Associated Oropharynx Cancer
Overview
- Phase
- Phase 2
- Intervention
- Docetaxel
- Conditions
- Human Papillomavirus Infection
- Sponsor
- Mayo Clinic
- Enrollment
- 81
- Locations
- 2
- Primary Endpoint
- 2-year Loco-regional Tumor Control (LRC) Rate
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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.)
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
Arms & Interventions
Treatment (docetaxel, hyperfractionated IMRT)
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.
Intervention: Docetaxel
Treatment (docetaxel, hyperfractionated IMRT)
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.
Intervention: Hyperfractionation
Treatment (docetaxel, hyperfractionated IMRT)
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.
Intervention: Intensity-Modulated Radiation Therapy
Treatment (docetaxel, hyperfractionated IMRT)
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.
Intervention: Laboratory Biomarker Analysis
Treatment (docetaxel, hyperfractionated IMRT)
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.
Intervention: Quality-of-Life Assessment
Outcomes
Primary Outcomes
2-year Loco-regional Tumor Control (LRC) Rate
Time Frame: 2 years
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.
Secondary Outcomes
- 2-year Distant Metastasis-free Survival Rate(2 years)
- 2-year Progression-free Survival (PFS)(From registration to the first of either disease recurrence or death, assessed up to 2 years)
- Incidence of Grade 3 or Higher Mucositis Oral(4 months post-hyperfractionated radiation therapy)
- 2-year Overall Survival (OS) Rate(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.(12 months)
- European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35)(1 year post-treatment)
- EuroQol Five-dimensional Instrument (EQ-5D-3L)(1 year post-treatment)
- Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (Version 4)(1 year)