Involved Field Elective Volume De-Intensification Radiation Therapy for Head and Neck Cancer

Study Overview
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Brief Summary
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Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel)

Detailed Description
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This study aims to significantly improve the acute and late morbidity of patients with oropharyngeal and laryngeal squamous cell carcinoma both by tailoring the elective irradiation only to regions with a legitimate risk of recurrence (> 5%) and by lowering the elective dose to 40 Gy. Level IB will not be electively treated unless it is involved with pathologic or suspicious lymphadenopathy. Level V will not be treated unless two or more ipsilateral nodal levels are involved (or level V itself has pathologic or suspicious adenopathy). Levels III and IV will only be irradiated if the immediately proximal level contains pathologic lymphadenopathy (i.e. level III irradiated if level II is positive; level IV irradiated if level III is positive). We anticipate that this approach should dramatically improve the acute and late complication profile.

Official Title
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A Prospective Phase II Study of Involved Field Elective Volume De-Intensification for Oropharyngeal and Laryngeal Squamous Cell Carcinoma Treated With Intensity Modulated Radiation Therapy

Conditions
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Head and Neck Cancer, Carcinoma, Squamous Cell, Neoplasms, Oral, Neoplasms, Pharyngeal

Intervention / Treatment
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* Radiation: Intensity Modulated Radiation Therapy
* Drug: chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically-proven diagnosis of squamous cell carcinoma of the oropharynx or larynx. Squamous cell carcinoma of unknown primary is not allowed. Patients must have clinically or radiographically evident measureable disease at the primary site and/or nodal stations. Patients may undergo a diagnostic tonsillectomy, and diagnostic lymph node excision (< 2 nodes) is also allowable. Clinical stage I-IVB (AJCC, 7th edition); stages I-II glottic cancer are excluded Age ≥ 18 years. ECOG Performance Status 0-2 Adequate organ and marrow function as defined below: leukocytes ≥ 3,000/mcL absolute neutrophil count ≥ 1,500/mcL platelets ≥ 100,000/mcl total bilirubin within normal institutional limits AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Negative serum or urine pregnancy test within 2 weeks before registration for women of childbearing potential. Neck CT and/or neck MRI, and whole body PET-CT. Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: Distant metastasis or adenopathy below the clavicles. Inability to undergo PET-CT. Stage I and II glottic carcinoma. Gross total excision of both the primary and nodal disease. Synchronous primaries outside of the oropharynx and larynx. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease-free for a minimum of 1 years Prior systemic chemotherapy for the study cancer; prior chemotherapy for a remote cancer is allowable Prior radiotherapy to the region of the study cancer that would result in overlap of radiation fields. Subjects may not be receiving any other investigational agents. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the chemotherapy agents in this study (if necessary). 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. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. History of immunosuppression or autoimmunity, including HIV, and organ or stem cell transplant, or an autoimmune condition previously treated with immunosuppressive therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Interventional Model Description: radiation therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiation Therapy<br>Intensity modulated radiation therapy (IMRT) with or without chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) | Radiation: Intensity Modulated Radiation Therapy<br>* The radiotherapy plan wil be delivered in 2 sequential courses. The first course involves 20 fractions of 2 Gy per fraction to the entire volume (gross disease and elective). The second course involves 15 fractions (thus, total of 35 fractions), at either 2 Gy (gross disease) or 1.6 Gy (microscopic disease and suspicious node) per fraction.<br>* Other names: IMRT;Drug: chemotherapy<br>* chemotherapy (if given, either cisplatin, cetuximab, or carboplatin-paclitaxel) per physician discretion<br>* Other names: cisplatin, cetuximab, or carboplatin-paclitaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Solitary Elective Volume Recurrence | The crude risk of 2-year solitary elective volume recurrence will be calculated among all patients who are followed for at least 2 years. Patients who die before 2 years without an SEVR will be included in the denominator. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (QOL) Patient Reported Outcomes (PRO) | Quality of life (QOL) patient-reported outcomes (PRO) for overall number of participants following treatment with elective volume and dose de-escalation, using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), EORTC HN35, which is specific to head and neck cancer, and composite MD Anderson Dysphagia Inventory (MDADI). EORTC QLQ-C30 and QLQ-H&N35 are scored on a 4-point categorical scale ranging from 1 not at all to 4 very much. This scale is then linearly transformed to a 0-100 scale, where a higher score represents a higher response level. A high score for a functional scale represents higher level functioning, a high score for quality of life represents a high quality of life, and a high score for a symptom scale represents worse symptoms. MD Anderson Dysphagia Inventory (MDADI) questionnaire: Possible score ranges from 0-100, with higher score indicating higher functioning. | 12 months | 
| Number of Participants With Definite, Possible, and Probable Protocol-related Toxicities (Grade 3-5) | Only adverse events (grade 3-5) assessed to be definitely, probably, or possibly related to protocol treatment up to 2 years post-treatment will be considered. This was measured according to NCI's CTCAE v4.0 toxicity criteria. | 2 years | 
| Total Number of Participants With Gastrostomy Dependence | The prevalence of gastrostomy use up to 2 years will be described. | 2 years | 
| Patient Utilities | The average patient utilities (derived from EQ-5D) from baseline up to 2 years from the end of treatment will be described. Changes in patient utility will be analyzed using generalized estimated equations (GEE). | 2 years | 
| Overall Survival | Overall survival will be calculated from the initiation of treatment using the Kaplan-Meier method. | 2 years | 
| Progression-free Survival | Progression-free survival will be calculated from the initiation of treatment. Progression is confirmed by biopsy, which will be used as the date of progression. | 2 year | 
| Probability of Locoregional or Distant Tumor Failure | The percentage of patients with locoregional or distant failure within 2 years of treatment will be estimated using cumulative incidence statistics, with death serving as the competing risk. Cumulative incidence refers to the estimated risk/probability of tumor failure within 2 years of treatment, either locoregional recurrence or distant metastasis, accounting for the competing risk of death. | 2 years |