Study of De_Intensified Postoperative Radiation Therapy for HPV Associated Oropharyngeal Squamous Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
This research study is studying lowering the standard dose of radiation and chemotherapy after surgery, to minimize the side effects and improve the quality of life.

Detailed Description
-----------------
This research study is being done to study if less intensive treatments can be used after surgery for head and neck cancers that are due to the human papilloma virus (HPV). In general, these cancers have better cure rates than other types of head and neck cancers. Therefore, the investigators are studying whether we can safely reduce the amount of treatment after surgery, such as surveillance (instead of using radiation) or less radiation or less chemotherapy, while maintaining good cure rates. The investigators hope that by reducing the intensity of treatment, this will lead to less side effects during and after cancer treatment.

Official Title
-----------------
A Phase 2 Study of De-Intensified Risk-Adapted Postoperative Radiation Therapy for Human Papilloma Virus Associated Oropharyngeal Squamous Cell Carcinoma: the ADAPT Trial

Conditions
-----------------
Head and Neck Cancer

Intervention / Treatment
-----------------
* Radiation: Radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed squamous cell carcinoma of the tonsil or base of tongue (oropharynx) or unknown primary with p16-positive cervical lymph node metastases HPV-associated tumor as defined by: positive p16 immunohistochemistry (>70%) OR in situ hybridization OR PCR-based methods Eligible for curative-intent surgery with anticipated negative margins Surgery performed at Brigham & Women's Hospital Age 18 or older years. ECOG performance status 0-1 (Karnofsky ≥70%, see Appendix A) Normal organ and marrow function as defined below: leukocytes ≥3,000/mcL absolute neutrophil count ≥1,000/mcL platelets ≥100,000/mcL total bilirubin within normal institutional limits AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine ≤ 1.5 times the institutional upper limit of normal OR creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal. Patients with ≤20 pack-years of cumulative cigarette smoking. Pack-years are calculated by multiplying the number of years smoked with the pack of cigarettes smoked per day. One pack is considered to contain 20 cigarettes. Tumor clinical stage (AJCC 8th edition): T0 or T1 or T2 Nodal clinical stage (AJCC 8th edition): N0 or N1 No distant metastases. Clinical M-stage must be M0 (AJCC 8th edition). Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Prior history of head and neck cancer within 5 years. Prior head and neck radiation Clinically fixed or matted nodes 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. Note: that HIV positive patients will be eligible. Pregnant women are excluded from this study because of the teratogenic risks of radiation exposure to the developing fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with radiation therapy and supportive care medications required for symptomatic management of head and neck cancer side effects as well as general anesthesia required for oncologic head and neck surgery, breastfeeding should be discontinued if the mother is enrolled in the study. Pregnancy status will be determined by a serum pregnancy test.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Risk<br>Observation without adjuvant therapy Pathologic T0-2, N0-1 Minimum of 15 lymph nodes retrieved on neck dissection per dissected side of the neck -≤2 positive lymph nodes confined to level II and/or level III No extranodal extension Clear margins | Radiation: Radiation therapy<br>* Radiation therapy<br>|
| Experimental: Intermediate Risk<br>Reduced-dose radiation (46Gy) Pathologic T0-2N0-2 and any one of the following features: ->2 positive lymph nodes <15 lymph nodes retrieved on neck dissection for each side of the neck Positive lymph nodes in level IB, IV, or V -≤1mm extranodal extension Positive lymph node(s) contralateral to the primary tumor Close margins | Radiation: Radiation therapy<br>* Radiation therapy<br>|
| Experimental: High Risk<br>Postoperative radiation (60Gy) without chemotherapy Pathologic T0-4N0-2 and any one of the following features: ->1mm extranodal extension Microscopic positive margins | Radiation: Radiation therapy<br>* Radiation therapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | Survival without any signs or symptoms of cancer after the treatment ends. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | The length of time from the start of treatment until death. | 2 years | 
| Toxicity Rate | Adverse events experienced by the participants. | 2 years | 
| Quality Of Life Questionnaire | Assesses the physical; social/family; emotional and functional wellbeing, using Functional Assessment of Cancer Therapy for Head and Neck (FACT-H&N) on a scale of 0-4 (where 0 indicates the lowest quality of life and 4 indicates the highest quality of life). | 2 Years | 
| Symptom burden: | Patient-reported symptom severity, using M.D. Anderson Symptom Inventory - Head & Neck (MDASI-HN) on a scale of 0-10 (where 0 indicates symptom is not present and 10 indicates the symptom is as bad as can be) | 2 years | 
| Dysphagia | Swallowing ability or difficulty. Dysphagia-related quality of life, assessed with the MD Anderson Dysphagia Inventory (MDADI) on a scale of 1-5 (where 1 indicates the patient strongly agrees and 5 indicates the patient strongly disagrees) | 2 Years | 
| Shoulder dysfunction | Shoulder function or dysfunction is measured with the neck dissection impairment index (NDII). This evaluates how much the patient's neck and/or shoulder affects them as a result of the treatment they received in their neck during the overall management of their cancer. This scale goes from 1-5 (1 being not at all and 5 being a lot) | 2 Years |