Post Operative Adjuvant Therapy De-intensification Trial for Human Papillomavirus-related, p16+ Oropharynx Cancer

Study Overview
=================
Brief Summary
-----------------
This clinical trial studies the intensity of adjuvant (helper) therapy required in p16 positive oropharynx cancer patients, who have had all known disease removed surgically by a minimally invasive approach, and who have extracapsular spread in their lymph nodes. Patients can consent to participate in either the randomized (physician chooses radiotherapy arm or radiotherapy & cisplatin arm) or non-randomized (patient chooses radiotherapy arm or radiotherapy & cisplatin arm) pathways. After the surgery, receive either radiation alone, or radiation and weekly cis-platinum during therapy. Patients are then followed for cancer, functional and quality of life outcomes.

Official Title
-----------------
Adjuvant De-escalation, Extracapsular Spread, P16+, Transoral (ADEPT) Trial for Oropharynx Malignancy

Conditions
-----------------
Oropharyngeal Neoplasms

Intervention / Treatment
-----------------
* Radiation: Intensity-modulated radiation therapy (IMRT)
* Drug: Cisplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient must have histologically confirmed p16 positive squamous cell carcinoma of the oropharynx (OPSCC). Patient must have undergone transoral resection of their T1-4a oropharynx primary to a negative margin, and a neck dissection(s). Patient's disease must be pathological N-stage positive. Patient's disease must show extracapsular spread (ECS) in their nodal metastasis verified by central pathologist's review. Patients with synchronous primaries are included. Patients with unknown primaries are included if the diagnosis and resection of a primary site in the oropharynx is made from an endoscopic or robotic surgical procedure(s). Patients with recent excisional node biopsies/neck dissections are included if material is evaluable for extracapsular spread. Patient must be ≥ 21 years of age. ECOG performance status ≤ 2 (Karnofsky ≥60%). Patients must have normal organ and marrow function as defined below: leukocytes ≥3,000/mcL absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total bilirubin <1.5 X upper normal institutional limit AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal Patient (or legally authorized representative) must be able to understand and willing to sign a written informed consent document. Exclusion Criteria: Patient must not have pathologically N stage negative disease. Patient must not have outside nodal tissue from previous neck biopsy/neck dissections in which ECS cannot be confirmed or denied. Patient must not have a true unknown primary in which permanent section results are negative for malignancy in completely excised ipsilateral oropharyngeal tissue (palatine and lingual tonsil). Patient must not have distant metastatic disease at presentation. Patient must not have gross residual and/or microscopic disease present after surgery including re-resection(s), per the operative and pathology report. Patient must not have transoral robotic surgery (TORS) for a T3 or T4 primary tumor. Patient must not have a history of prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; noninvasive cancers (for example, carcinoma in situ of the oral cavity, larynx, breast or cervix are all permissible) are permitted even if diagnosed and treated < 3 years ago. Patient must not have had previous systemic chemotherapy for the study cancer. (Note: prior chemotherapy for a different cancer is allowable). Patient must not be receiving any other investigational agents. Patient must not have had any prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields Patient must not have any life-threatening comorbid illnesses e.g. stroke with major sequelae or myocardial infarction/ unstable angina within the preceding 3 months or psychiatric illness/social situations that would limit compliance with study requirements. Patient must not be pregnant or breastfeeding. If a woman of childbearing potential, patient must agree to use medically acceptable forms of contraception. Both men and women and members of all races and ethnic groups are eligible for this trial.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiotherapy<br>Patients undergo postoperative IMRT once daily, 5 days a week, for 6 weeks. The prescribed radiotherapy dose will be 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions). Patients can consent to participate in either the randomized (physician chooses radiotherapy arm or radiotherapy & cisplatin arm) or non-randomized (patient chooses radiotherapy arm or radiotherapy & cisplatin arm) pathways | Radiation: Intensity-modulated radiation therapy (IMRT)<br> <br> |
| Active Comparator: Radiotherapy, cisplatin<br>Patients undergo postoperative IMRT once daily, 5 days a week, for 6 weeks. The prescribed radiotherapy dose will be 60 Gy in 2 Gy once-daily fraction size (total of 30 fractions) Patients also receive cisplatin 40 mg/m2 IV on Days 1, 8, 15, 22, 29, and 36 of radiation therapy (6 doses for a total of 240 mg/m2). Patients can consent to participate in either the randomized (physician chooses radiotherapy arm or radiotherapy & cisplatin arm) or non-randomized (patient chooses radiotherapy arm or radiotherapy & cisplatin arm) pathways | Radiation: Intensity-modulated radiation therapy (IMRT)<br> <br> Drug: Cisplatin<br> <br> * Other names: CACP, CDDP, CPDD, DDP, Neoplatin;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Disease-free Survival (DFS) |  | 1 year | 
| Locoregional Control | Rate of patients with no recurrence at original oropharyngeal site or in the neck nodal basins. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Distant Metastasis | Assessed by biopsy or imaging-detected recurrent disease at sites away from the original primary and cervical zone. | Up to 2 years | 
| Disease Specific Survival |  | 1 year | 
| Number of Complications/Acute Toxicity by Organ Class | -Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | Approximately 18 weeks | 
| Change in Quality of Life as Measured by the MD Anderson Dysphagia Inventory | Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree). Strongly agree = 1, Disagree = 2, No opinion = 3, Agree = 4, and Strongly Agree = 5 The lower the score the lower the quality of life | Baseline, 1 month, 6 months, 12 months, and 24 months | 
| Change in Cognitive Function as Measured by Cognitive Failures Questionnaire | 25 questions to assess the frequency in which participants experience cognitive failures including forgetfulness, distractibility, and false triggering Answers range from 0 = never to 4 = very often The higher the score the worse the cognitive failures the participant has experienced | Baseline, 1 month, 12 months, and 24 months | 
| Change in Quality of Life as Measured by Neck Dissection Impairment Index (NDII) | -The NDII consists of 10 questions; each with a 5 level ordinally scaled response option ranging from not at all to a lot. The response for each item is then scored from 1 to 5, with 5 denoting higher quality of life (Not at all) and 1 being the least (A lot). | Baseline, 12 months, and 24 months | 
| Change in Quality of Life as Measured by University of Michigan Xerostomia Questionnaire | It contains 8 questions regarding dryness either during feeding or in the unstimulated state. Participants rate each item from 0 to 10, where 10 indicates the maximum dryness or discomfort due to dryness. The higher the score the worse the participant's xerostomia | Baseline, 1 month, 6 months, 12 months, and 24 months | 
| Change in Hearing as Measured by Hearing Handicap Inventory - Adult | 11 item questionnaire to identify issues with hearing Answers are yes = 4, sometimes = 2, and no = 0 The higher the score the more issues the participant has with hearing | Baseline, 1 month, and 12 months | 
| Change in Quality of Life as Measured by Scale of Subjective Total Taste Acuity | 1 question that asks about taste acuity Answers are 0 = same taste acuity as before treatment; 1 = mild loss of taste acuity, but not inconvenient in daily life; moderate loss of taste acuity, and sometimes inconvenient in daily life; severe loss of taste acuity, and frequently inconvenient in daily life; and 4 = almost complete or complete loss of taste acuity The higher the score the worse the participant's taste acuity | Baseline, 1 month, 6 months, and 12 months | 
| Change in Quality of Life as Measured by Speech Handicap Index | 31 questions regarding participant's speech and the effects of speech on his/her life The answers for the first 30 questions range from 0 = never to 4 = always and the answers for the 31st question ranges from 0 = excellent to bad = 4 The higher the score the worse the participant's speech is affecting his/her life | Baseline and 12 months | 
| Change in Quality of Life as Measured by EORTC QLQ-C30 | 30 questions designed to assess the quality of life of cancer patients The first 28 questions have answers that range from 1=not at all to 4 = very much. The higher score indicates a worse quality of life The last 2 questions have answers that range from 1 = very poor to 7 = excellent. The higher score indicates a better quality of life | Baseline, 1 month, 6 months, 12 months, and 24 months |