Stereotactic Body Radiation Therapy in Treating Patients With High Risk Locally Advanced Head and Neck Cancer

Study Overview
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Brief Summary
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This phase I trial studies the side effects and best dose of stereotactic body radiation therapy (SBRT) in treating participants with head and neck cancer that has spread from where it started to nearby tissue or lymph nodes and is at high risk for continuing to spread because the participant cannot undergo standard chemotherapy. Stereotactic body radiation therapy is a specialized radiation therapy that delivers radiation directly to the tumor in smaller doses over several days, which may kill more tumor cells and cause less damage to normal tissue.

Detailed Description
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PRIMARY OBJECTIVES: I. To explore the maximum tolerated dose of head and neck stereotactic body radiation therapy (SBRT) in a high risk participant population ineligible for standard chemoradiotherapy. SECONDARY OBJECTIVES: I. Assess profiles of SBRT toxicity and examine participant (including co-morbidities), tumor and treatment related factors that are associated with SBRT related toxicity. II. Identify any dose volume parameters that are associated with SBRT related toxicity. III. Explore potential dose response relationships between higher SBRT dosing and radiographic response. IV. Assess impact of SBRT on participants' quality of life. OUTLINE: This is a dose-escalation study. Participants undergo SBRT in 5 fractions at least 40 hours apart over 10-18 days. After completion of study treatment, participants are followed up at 0.5, 3, 6, 9, and 12 months.

Official Title
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Phase I Dose Escalation Study of Stereotactic Body Radiotherapy for Carcinoma of the Head and Neck in High Risk Patients Who Are Ineligible/Refuse Standard of Care Therapy

Conditions
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Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma, Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Recurrent Oral Cavity Squamous Cell Carcinoma, Recurrent Oropharyngeal Squamous Cell Carcinoma, Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Stage III Hypopharyngeal Squamous Cell Carcinoma, Stage III Laryngeal Squamous Cell Carcinoma, Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma, Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Stage III Oral Cavity Squamous Cell Carcinoma, Stage III Oropharyngeal Squamous Cell Carcinoma, Stage IVA Hypopharyngeal Squamous Cell Carcinoma, Stage IVA Laryngeal Squamous Cell Carcinoma, Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Stage IVA Oral Cavity Squamous Cell Carcinoma, Stage IVA Oropharyngeal Squamous Cell Carcinoma, Stage IVB Hypopharyngeal Squamous Cell Carcinoma, Stage IVB Laryngeal Squamous Cell Carcinoma, Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma, Stage IVB Oral Cavity Squamous Cell Carcinoma, Stage IVB Oropharyngeal Squamous Cell Carcinoma, Stage IVC Hypopharyngeal Squamous Cell Carcinoma, Stage IVC Laryngeal Squamous Cell Carcinoma, Stage IVC Oral Cavity Squamous Cell Carcinoma, Stage IVC Oropharyngeal Squamous Cell Carcinoma

Intervention / Treatment
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* Radiation: Stereotactic Body Radiation Therapy
* Device: Positron Emission Tomography
* Device: Computed Tomography
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant must have squamous cell carcinoma proven by histologic diagnosis; for cancers of the oropharynx, p16 staining by immunohistochemistry must be negative; for cancers of the larynx, hypopharynx, oral cavity, nasopharynx, paranasal sinuses, p16 staining is not required The participant must have clinical stage T1-4, N0-3, M0-1, stage II-IVC carcinoma as per the 7th edition of the American Joint Committee on Cancer (AJCC) staging manual; participants with T1N0M0 will be ineligible; participants with metastatic disease with a limited metastatic burden are eligible if obtaining local control is determined by their treating oncologist to be an important therapeutic goal The participant must have imaging documenting a primary tumor, or involved lymph node, ≥ 2.5 cm in greatest dimension PET/CT is required for all participants, unless contraindicated; this may be acquired prior to study entry or after enrollment prior to SBRT planning The participant must have a history and physical documented within four weeks of registration and be deemed by a medical oncologist to be ineligible for standard continuous course chemoradiotherapy with cisplatin Karnofsky performance status (PS) ≥ 40 Female participants cannot be of childbearing age, or if they are, must have a negative pregnancy test prior to enrollment and be willing to use contraceptives during treatment and continue for 6 additional months Participants must have the ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Participants with T1N0M0 stage I disease Participants who are receiving any other investigational agents Participants with non-squamous cell histology Participants with life expectancy < 6 months Participants who cannot lie flat for 20 minutes Participants with prior history of head and neck radiotherapy (> 40 Gy) with significant areas of anticipated overlap

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 (SBRT)<br>Participants undergo Stereotactic Body Radiation Therapy in 5 fractions at least 40 hours apart over 10-18 days. Three dose levels: 40Gy and 45Gy all in 5 fractions. Each initial dose level will have 6 participants allocated to them. All participants are assessed at their 3 month post SBRT visit for Dose-Limiting Toxicities (DLTs). If ≤1 participant experiences a DLT, participants will be enrolled at the next dose level. If ≥3 participants experience a DLT, further accrual will be permanently halted and the study stopped. If 2 participants experience a DLT, then an additional 6 participants will be enrolled at the same dose level. In this setting, if ≤ 3/12 participants have a DLT, participants will be enrolled at the next dose level. If ≥ 4/12 participants have a DLT, further accrual will be permanently halted and the study stopped and 35 Gy will not be recommended as safe. The dosing strategy for the 2nd (45Gy) cohort will be identical to the first. | Radiation: Stereotactic Body Radiation Therapy<br>* Undergo SBRT<br>* Other names: SBRT;Device: Positron Emission Tomography<br>* Undergo PET/CT<br>* Other names: Positron Emission Tomography Scan;Device: Computed Tomography<br>* Undergo PET/CT<br>* Other names: CT;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 |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of Head and Neck SBRT | Maximum tolerated dose of SBRT in this patient population determined by the dose escalation design with doses '40Gy' and '45Gy all in 5 fractions'. | 3 months | 
| Incidence of Dose Limiting Toxicities (DLTs) | Number of patients with dose limiting toxicity events graded according to CTCAE Version 4.0 | 3 months from start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Kaplan-Meier estimates will be used to plot overall survival - the number of patients alive at 12 months followup | Up to 12 months | 
| Local Progression Free Survival | Kaplan-Meier estimates will be used to plot local progression free survival. | Up to 12 months | 
| Response Measured According to Standard Response Evaluation Criteria in Solid Tumors | Trend tests will be used to investigate the relationship between SBRT dose and response. | Up to 12 months | 
| Incidence of SBRT Related Morbidity | Number of patients who experiences SBRT-related morbidity according to NCI CTCAE v 4.0 | Up to 12 months | 
| Quality of Life Assessed by Functional Assessment of Cancer Therapy-Head and Neck Questionnaire | Repeated analysis of variance measures will be used to analyze the quality of life data. | Up to 12 months |