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

Not Applicable

Terminated

Conditions: Recurrent Hypopharyngeal Squamous Cell Carcinoma
Recurrent Oropharyngeal Squamous Cell Carcinoma
Stage III Hypopharyngeal Squamous Cell Carcinoma
Stage III Laryngeal Squamous Cell Carcinoma
Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma
Stage IVA Hypopharyngeal Squamous Cell Carcinoma
Stage IVB Laryngeal Squamous Cell Carcinoma
Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma
Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma
Stage III Oral Cavity Squamous Cell Carcinoma

Interventions: Radiation: Stereotactic Body Radiation Therapy
Device: Positron Emission Tomography
Device: Computed Tomography
Other: Quality-of-Life Assessment

Registration Number: NCT02388932

Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (SBRT)	Stereotactic Body Radiation Therapy	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.
Treatment (SBRT)	Positron Emission Tomography	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.
Treatment (SBRT)	Computed Tomography	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.
Treatment (SBRT)	Quality-of-Life Assessment	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.

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of Head and Neck SBRT	3 months	Maximum tolerated dose of SBRT in this patient population determined by the dose escalation design with doses '40Gy' and '45Gy all in 5 fractions'.
Incidence of Dose Limiting Toxicities (DLTs)	3 months from start of treatment	Number of patients with dose limiting toxicity events graded according to CTCAE Version 4.0

Secondary Outcome Measures

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

Trial Locations

Locations (2): Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
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Cleveland, Ohio, United States
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
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Cleveland, Ohio, United States