Randomized Trial of Intensity-Modulated Proton Beam Therapy (IMPT) Versus Intensity-Modulated Photon Therapy (IMRT) for the Treatment of Oropharyngeal Cancer of the Head and Neck

Baseline Visit:

If you are found to be eligible to take part in this study, you will have a baseline visit.
The following tests and procedures will be performed:

- You will be asked about your diet and if you have had recent weight loss.

- You will have a dental exam.

- Your swallowing function will be tested with a special type of x-ray called a modified
barium swallow (MBS). During the test, you will eat and drink foods and liquids mixed
with a "contrast" chemical called barium that will make your throat more visible in the
x-rays. A special x-ray tube will be connected to a television screen to allow the
doctor to watch the foods and liquids pass from your mouth and down your throat. As part
of this exam, each time you will fill out a questionnaire about swallowing that should
take about 5 minutes to complete.

- You will have a video-strobe procedure or laryngoscopy to allow the doctor to look at
your vocal cords. To perform a video-strobe procedure, a small camera will be inserted
into the throat through your nose or mouth. You will be awake for this procedure and the
study staff will give you the option of receiving a numbing spray for your nose and/or
throat. A laryngoscopy is a standard procedure in which a tube with a lighted camera is
inserted through your mouth and into your throat.

- Photos of the inside of your mouth will be taken to check for mouth sores.

- You will fill out questionnaires about your quality of life, work status, medical
history, smoking status, and any symptoms you may have. Completing these questionnaires
should take about 10-15 minutes. An email address will be collected for the transmitting
questionnaires. An email address will be collected for the transmitting questionnaires.

- Saliva will be collected and your jaw will be measured at this visit, at the end of your
treatment, and also during follow up for 2 years. You should be fasting for a minimum of
60 minutes and instructions regarding the collection will be given.

Study Groups:

You will go through the standard radiation treatment planning procedure, called the marking
session. After the marking session, a standard IMRT plan and an IMPT plan will be made. If
the radiation doctor thinks that both the plans are acceptable, you will be randomly assigned
(as a flip of a coin) to 1 of 2 study groups:

If you are in Group 1, you will receive IMRT.

If you are in Group 2, you will receive IMPT.

If you are assigned to Group 1 but do not receive the IMRT treatment, you will be moved to
Group 4. You will then have follow-up only to be asked about the status of the disease and
how you are doing, as explained below.

If you are assigned to Group 2 but do not receive the IMPT treatment, you will be moved to
Group 3. You will then have follow-up only to be asked about the status of the disease and
how you are doing.

Study Therapy Administration:

You will receive radiation therapy 1 time each day, 5 days a week (Monday through Friday) for
up to 33 treatments (about 6 ½ weeks).

You will receive chemotherapy while you are receiving radiation therapy. You will be asked to
sign a separate treatment consent form for these drugs with a full description of how they
are given and the risks they may cause. The drugs, schedule, and doses will be your doctor's
decision.

Study Visits:

Every week while you are receiving radiation therapy:

- Any updates to your medical history will be recorded.

- You will have a physical exam, including measurement of your vital signs and weight.

- Blood (about 1-2 tablespoons) will be drawn for routine tests.

- You will fill out the same questionnaires as before.

- At Week 3, photos of the inside of your mouth will be taken to check for mouth sores.

Length of Treatment:

You may continue receiving radiation therapy for up to 6 ½ weeks. You will no longer be able
to receive the study therapy if the disease gets worse, if intolerable side effects occur, or
if you are unable to follow study directions.

Your participation on the study will be over after you complete all the follow-up visits.

You can decide to stop taking part in this study and the study doctor will tell you how to
stop safely. It is important to tell the study doctor if you are thinking about stopping so
any side effects from the treatment can be looked at by your doctor. Another reason to tell
your doctor that you are thinking about stopping is to discuss what follow-up care and
testing could be most helpful for you.

End-of-Treatment Visit:

After you finish radiation therapy (at Week 7):

- You will fill out the same questionnaires as before.

- You will have a dental exam, including jaw measurements and collection of saliva.

- Photos of the inside of your mouth will be taken to check for mouth sores.

Follow-Up:

At 8-12 weeks after finishing radiation therapy:

- You will have a dental exam, including jaw measurements and collection of saliva.

- Photos of the inside of your mouth will be taken to check for mouth sores.

- If the doctor thinks it is needed, you will have a CT scan or PET/CT scan to check the
status of the disease.

During Follow-Up Months 6, 12, and 24:

- You will have an MBS exam to test your swallowing function.

- You will fill out the same questionnaires as before.

- Saliva and jaw measurements will be collected.

- Photos of the inside of your mouth will be taken to check for mouth sores.

- You will have a laryngoscopy or video-strobe procedure to allow the doctor to look at
your vocal cords.

- You will have a CT or PET scan.

During Follow-Up Months 9, 16, and 20:

- Saliva and jaw measurements will be collected.

- You will fill out the same questionnaires as before.

- You will have a CT or PET scan.

Every 6 months during Follow-Up Month 30 through Follow-Up Year 5:

- You will fill out the same questionnaires as before.

- You will have a CT or PET scan.

After you finish radiation therapy and during the 8-12 weeks while you are recovering from
treatment, you will be provided with a questionnaire, by email or in paper form, that asks
about any side effects you may have had. You will fill out this form every 2 weeks during
this time period. Filling out the form should take about 10-15 minutes.

Filling out these forms does not take the place of your regularly scheduled follow-up visits.
If you have side effects, you should also tell the study staff.

If the doctor thinks it is needed during follow-up, you will have a tumor biopsy for tumor
marker testing.

Inclusion Criteria:

1. Age >/= 18

2. Histologically documented Squamous Cell Carcinoma of the oropharynx (American Joint
Committee on Cancer (AJCC) v7** Stage III-IV A,B)

3. Tumor tissue (primary or cervical metastasis) available for human papilloma virus
(HPV) and/or p16 (in situ hybridization (ISH), immunohistochemistry (IHC) or
genotyping testing) If you do not have enough leftover tumor tissue available, you
will have a tumor biopsy for tumor marker testing.

4. Eastern Cooperative Oncology Group (ECOG) performance status= 0, 1, or 2

5. Negative pregnancy test for women of child bearing potential

6. Concurrent Chemotherapy

7. Bilateral Neck Radiation

Exclusion Criteria:

1. Previous radiation treatment for head and neck mucosal primary cancers within the past
5 years (i.e. oropharynx, nasopharynx, hypopharynx, larynx, and oral cavity)

2. Pregnant or breast-feeding females

3. Clinically significant uncontrolled major cardiac, respiratory, renal, hepatic,
gastrointestinal or hematologic disease but not limited to: a) Symptomatic congestive
heart failure, unstable angina, or cardiac dysrrhythmia not controlled by pacer
device. b) Myocardial infarction within 3 months of registration.

4. Distant Metastases (Stage IV C, any T, any N and M1)

5. Previous surgical resection or neck dissection for oropharyngeal cancer, administered
with therapeutic intent.