Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This randomized phase II trial studies how well transoral surgery followed by low-dose or
standard-dose radiation therapy works in treating patients with human papilloma virus (HPV)
positive stage III-IVA oropharyngeal cancer. Radiation therapy uses high-energy x-rays to
kill tumor cells. Drugs used in chemotherapy work in different ways to stop the growth of
tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation
therapy with chemotherapy may kill any tumor cells that remain after surgery. It is not yet
known how much extra treatment needs to be given after surgery.
Phase
Phase 2
Funding Agency/Sponsor
National Cooperative Group
Disease
Head and Neck Cancer
Enrollment Eligibility
Inclusion Criteria:
Registration to Surgery (Arm S)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Patients must have newly diagnosed, histologically or cytologically confirmed squamous
cell carcinoma or undifferentiated carcinoma of the oropharynx; patients must have
been determined to have resectable oropharyngeal disease; patients with primary tumor
or nodal metastasis fixed to the carotid artery, skull base or cervical spine are not
eligible
- Patients must have American Joint Committee on Cancer (AJCC) TNM tumor stage III, IV
a, or IV b (with no evidence of distant metastases) as determined by imaging studies
(performed < 30 days prior to pre-registration) and complete head and neck exam; the
following imaging is required: computed tomography (CT) scan with IV contrast or
magnetic resonance imaging (MRI)
- Patients must have biopsy-proven p16+ oropharynx cancer; the histologic evidence of
invasive squamous cell carcinoma may have been obtained from the primary tumor or
metastatic lymph node. It is required that patients have a positive p16 IHC (as
surrogate for HPV) status from either the primary tumor or metastatic lymph node.
- Carcinoma of the oropharynx associated with HPV as determined by p16 protein
expression using immunohistochemistry (IHC) performed by a Clinical Laboratory
Improvement Amendments (CLIA) approved laboratory; using p16 antibody obtained from
Roche mtm laboratories AG (CINtec, clone E6H4) is recommended
- Patients with a history of a curatively treated malignancy must be disease-free for at
least two years except for carcinoma in situ of cervix and/or non-melanomatous skin
cancer
- Patients with the following within the last 6 months prior to pre-registration must be
evaluated by a cardiologist and/or neurologist prior to entry into the study
- Congestive heart failure > NYHA Class II
- Cerebrovascular accident (CVA)/transient ischaemic attack (TIA)
- Unstable angina
- Myocardial infarction
- Absolute neutrophil count >= 1,500/mm^3
- Platelets >= 100,000/mm^3
- Total bilirubin =< the upper limit of normal (ULN)
- Calculated creatinine clearance must be > 60 ml/min using the Cockcroft-Gault formula
Registration/Randomization to Step2 - Arms A, B, C and D
- Histopathologic assessment of surgical pathology must include examination for
perineural invasion (PNI) and lymphovascular invasion (LVI) and reported as absent or
present; the absence or presence of extracapsular extension (ECE) requires gross and
microscopic assessment and is defined to be:
- Absent (negative or nodal metastasis with smooth/rounded leading edge confined to
thickened capsule/pseudocapsule),
- Present - minimal (tumor extends =< 1 mm beyond the lymph node capsule), or
- Present - extensive (gross, tumor extends > 1 mm beyond the lymph node capsule
(includes soft tissue metastasis)
- Patient must be stratified/classified into one of the following risk categories (the
highest risk feature assessed pathologically will determine the patient's
category/treatment arm assignment):
- Low Risk: T1-T2, N0-N1 AND clear (≥ 3mm) margins, AND no ECE or PNI/LVI
- High Risk: Any of the following features: one or more positive margin(s) with any
T stage, OR "Extensive" (> 1mm) ECE, OR ≥ 5 metastatic lymph nodes (regardless of
primary tumor margin status)
- Intermediate Risk: Any of the following features: one or more "close" (< 3mm)
margin(s), OR "Minimal" (≤ 1mm) ECE, OR N2a (1 or more lymph node > 3cm in
diameter), OR N2b (2-4 lymph nodes positive, any diameter ≤ 6cm), OR with
perineural invasion or lymphovascular invasion.
- Unknown Risk: Patients found to have N2C or N3 disease on final pathologic
analysis are at unknown risk for recurrence, but are not candidates for
deintensified adjuvant therapy in this trial. These patients will be treated on
Arm C.
- Patients not categorized into the appropriate risk category will be considered
ineligible for the study
- Patient must be registered/randomized to Step 2 within a maximum of 7 weeks following
surgery
- Women of childbearing potential and sexually active males are strongly advised to use
an accepted and effective method of contraception
Exclusion Criteria:
Registration to Surgery (Arm S)
- Prior radiation above the clavicles
- Evidence of extensive or "matted/fixed" pathologic adenopathy on preoperative imaging
- Women must not be pregnant or breast-feeding due to the teratogenicity of
chemotherapy; all females of childbearing potential must have a blood test or urine
study within 2 weeks prior to registration to rule out pregnancy; a female of
childbearing potential is any woman, regardless of sexual orientation or whether they
have undergone tubal ligation, who meets the following criteria: has not undergone a
hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for
at least 24 consecutive months (i.e., has had menses at any time in the preceding 24
consecutive months)
- Any intercurrent illness likely to interfere with protocol therapy or prevent surgical
resection
- Uncontrolled diabetes, uncontrolled infection despite antibiotics or uncontrolled
hypertension within 30 days prior to pre-registration