Reduced-Dose Intensity-Modulated Radiation Therapy With or Without Cisplatin in Treating Patients With Advanced Oropharyngeal Cancer

PRIMARY OBJECTIVES:

I. To select the arm(s) achieving a 2-year progression-free survival rate of >= 85% without
unacceptable swallowing toxicity at 1 year.

SECONDARY OBJECTIVES:

I. To determine patterns of failure (locoregional relapse versus distant) and survival
(overall and progression-free) at 6 months and 2 years.

II. To determine acute toxicity profiles at the end of radiation therapy and at 1 and 6
months.

III. To determine late toxicity profiles at 1 and 2 years. IV. To determine patient-reported
swallowing outcomes at 6 months and 1 and 2 years.

V. To determine the predictive value of 12-14 week, post-treatment fludeoxyglucose F 18
(FDG)-positron emission tomography (PET)/computed tomography (CT) for locoregional control
and progression free survival (PFS) at 2 years.

VI. To determine the predictive value of blood and tissue biomarkers for disease outcomes at
2 years.

VII. To determine swallowing recovery per videofluoroscopy imaging at 2 years.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo IMRT once daily (QD) five days a week for 6 weeks to a total dose of
60 Gy and receive cisplatin intravenously (IV) over 30-60 minutes weekly during radiation
therapy for 6 doses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients undergo IMRT five days a week for 5 weeks to a total dose of 60 Gy in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months for 3 years, and then annually thereafter.

Inclusion Criteria:

- STEP 1: REGISTRATION

- Pathologically (histologically or cytologically) proven diagnosis of squamous cell
carcinoma (including the histological variants papillary squamous cell carcinoma and
basaloid squamous cell carcinoma) of the oropharynx (tonsil, base of tongue, soft
palate, or oropharyngeal walls); cytologic diagnosis from a cervical lymph node is
sufficient in the presence of clinical evidence of a primary tumor in the oropharynx;
clinical evidence should be documented, may consist of palpation, imaging, or
endoscopic evaluation, and should be sufficient to estimate the size of the primary
(for T stage)

- Patients must have clinically or radiographically evident measurable disease at the
primary site or at nodal stations; tonsillectomy or local excision of the primary
without removal of nodal disease is permitted, as is excision removing gross nodal
disease but with intact primary site; limited neck dissections retrieving =< 4 nodes
are permitted and considered as non-therapeutic nodal excisions

- Immunohistochemical staining for p16 must be performed on tissue, and this tissue must
be submitted for central review; fine needle aspiration (FNA) biopsy specimens may be
used as the sole diagnostic tissue if formalin-fixed paraffin-embedded cell block
material is available for p16 immunohistochemistry; FNA specimens prepared with
adequate p16 testing in this manner are acceptable to submit for central review; if
the p16 preparation is not adequate, additional specimens will be required to
establish p16 status; centers are encouraged to contact the pathology chairs for
clarification

- Clinical stage T1-T2, N1-N2b or T3, N0-N2b (American Joint Committee on Cancer [AJCC],
7th edition [ed.]) including no distant metastases based on the following diagnostic
workup:

- General history and physical examination within 56 days prior to registration

- Fiberoptic exam with laryngopharyngoscopy (mirror and/or fiberoptic and/or direct
procedure) within 70 days prior to registration

- One of the following combinations of imaging is required within 56 days prior to
registration:

- A CT scan of the neck (with contrast) and a chest CT scan (with or without
contrast)

- Or a magnetic resonance imaging (MRI) of the neck (with contrast) and a
chest CT scan (with or without contrast)

- Or a CT scan of neck (with contrast) and a PET/CT of neck and chest (with or
without contrast)

- Or an MRI of the neck (with contrast) and a PET/CT of neck and chest (with
or without contrast)

- Note: a CT scan of neck and/or a PET/CT performed for the purpose of
radiation planning may serve as both staging and planning tools

- Patients must provide their personal smoking history prior to registration; the
lifetime cumulative history cannot exceed 10 pack-years; the following formula is used
to calculate the pack-years during the periods of smoking in the patient's life; the
cumulative total of the number of pack-years during each period of active smoking is
the lifetime cumulative history

- Number of pack-years = (frequency of smoking [number of cigarettes per day] x
duration of cigarette smoking [years])/20

- Note: twenty cigarettes is considered equivalent to one pack; the effect of
non-cigarette tobacco products on the survival of patients with p16-positive
oropharyngeal cancers is undefined; cigar and pipe tobacco consumption is
therefore not included in calculating the lifetime pack-years; marijuana
consumption is likewise not considered in this calculation; there is no clear
scientific evidence regarding the role of chewing tobacco-containing products in
this disease; investigators are discouraged from enrolling patients with a
history of very sustained use (such as several years or more) of non-cigarette
tobacco products alone

- Zubrod performance status of 0-1 within 56 days prior to registration

- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

- Platelets >= 100,000 cells/mm^3

- Hemoglobin >= 8.0 g/dl; Note: the use of transfusion or other intervention to achieve
hemoglobin (Hgb) >= 8.0 g/dl is acceptable

- Serum creatinine =< 1.5 mg/dl or creatinine clearance (CC) >= 50 ml/min determined by
24-hour collection or estimated by Cockcroft-Gault formula

- Bilirubin =< 2 mg/dl

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x the upper
limit of normal

- Negative serum pregnancy test within 14 days prior to registration for women of
childbearing potential

- Patients who are human immunodeficiency virus (HIV) positive but have no prior
acquired immune deficiency syndrome (AIDS)-defining illness and have cluster of
differentiation (CD)4 cells of at least 350/mm^3 are eligible; HIV-positive patients
must not have multi-drug resistant HIV infection or other concurrent AIDS-defining
conditions; patients must not be seropositive for hepatitis B (hepatitis B surface
antigen positive or anti-hepatitis B core antigen positive) or seropositive for
hepatitis C (anti-hepatitis C antibody positive); however, patients who are immune to
hepatitis B (anti-hepatitis B surface antibody positive) are eligible (e.g. patients
immunized against hepatitis B)

- The patient must provide study-specific informed consent prior to study entry,
including consent for mandatory submission of tissue for required, central p16 review

- Patients who speak English (or read one of the languages for which a translation is
available must consent to complete the mandatory dysphagia-related patient reported
instrument (MDADI); if the patient cannot understand spoken English and reads only
languages not available in the MDADI translations, the patient can still participate
in the trial, as this has been factored into the trial statistics; for all other
patients, the MDADI is mandatory as it is included in the primary endpoint to be
studied

- STEP 2: RANDOMIZATION

- p16 positive by immunohistochemistry (defined as greater than 70% strong nuclear or
nuclear and cytoplasmic staining of tumor cells, confirmed by central pathology
review)

Exclusion Criteria:

- STEP 1 (REGISTRATION)

- Cancers considered to be from an oral cavity site (oral tongue, floor mouth, alveolar
ridge, buccal or lip), or the nasopharynx, hypopharynx, or larynx, even if p16
positive, or histologies of adenosquamous, verrucous, or spindle cell carcinomas

- Carcinoma of the neck of unknown primary site origin (even if p16 positive)

- Radiographically matted nodes, defined as 3 abutting nodes with loss of the
intervening fat plane

- Supraclavicular nodes, defined as nodes visualized on the same axial imaging slice as
the clavicle

- Definitive clinical or radiologic evidence of metastatic disease or adenopathy below
the clavicles

- Gross total excision of both primary and nodal disease with curative intent; this
includes tonsillectomy, local excision of primary site, and nodal excision that
removes all clinically and radiographically evident disease; in other words, to
participate in this protocol, the patient must have clinically or radiographically
evident gross disease for which disease response can be assessed

- Patients with simultaneous primary cancers or separate bilateral primary tumor sites
are excluded with the exception of patients with bilateral tonsil cancers

- Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
for a minimum of 1095 days (3 years) (for example, carcinoma in situ of the breast,
oral cavity, or cervix are all permissible)

- Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a
different cancer is allowable

- Prior radiotherapy to the region of the study cancer that would result in overlap of
radiation therapy fields

- Severe, active co-morbidity defined as follows:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within the last 6 months

- Acute bacterial or fungal infection requiring intravenous antibiotics at the time
of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days of
registration

- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
note, however, that laboratory tests for liver function and coagulation
parameters are not required for entry into this protocol other than those
requested

- Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease
Control and Prevention (CDC) definition; note, however, that HIV testing is not
required for entry into this protocol; protocol-specific requirements may also
exclude immuno-compromised patients

- Pregnancy

- Prior allergic reaction to cisplatin