This is a single arm phase II study that will enroll patients with HPV-associated
oropharyngeal cancer, undergoing resection through trans-oral robotic surgery (TORS) of all
gross visible disease at the primary site and in the lymph nodes. A total of 36 patients at
Cedars-Sinai Medical Center and its affiliates (Tower Hematology-Oncology, Torrance Memorial
Physician Network) who have had or will require surgery to remove cancer cells prior to
starting chemoradiation may be enrolled. All eligible patients will receive de-intensified
cisplatin-based chemoradiation, with high-risk patients receiving a higher dose and longer
treatment period than other patients on the study. The treatment period will last 3 to 5
weeks depending on whether the patient is considered high-risk or not. The study will assess
whether a de-intensified version of standard chemoradiation treatment will be just as
effective in treating HPV-associated oropharyngeal cancer while causing less side effects
than standard dosing.
Inclusion Criteria:
1. AJCC 8th edition T0-3N0-2 p16-positive oropharyngeal (tonsil, base of tongue,
glossotonsillar sulcus, soft palate, oropharyngeal wall) squamous cell carcinoma or
squamous cell carcinoma of unknown primary involving the cervical lymph nodes.
Cytologic diagnosis from a cervical lymph node is sufficient for diagnosis in the
presence of clinical evidence of a primary tumor in the oropharynx.
2. For patients with pT0 tumors (unknown primary), there must be at least one metastatic
lymph node present in cervical level II.
3. p16 should be strongly and diffusely positive in the nuclear and cytoplasmic component
in greater than 70% of the tumor cells.
4. Have undergone or will undergo gross total resection of all known disease in the head
and neck via transoral robotic surgery. For patients with unknown primary tumors, a
minimum of an ipsilateral tonsillectomy and base of tongue resection is required.
5. Have undergone or will undergo neck dissection.
6. Have at least one of the following after surgery:
- Pathologic stage T3
- 2 or more positive lymph nodes
- At least one lymph node >3cm
- Lymphovascular invasion
- Perineural invasion
- Extranodal extension
- Close/positive margins: Close margins are considered <3mm from the peripheral
margins and <1mm from the deep margin on the en bloc specimen, unless the area of
close margin is re-resected and without carcinoma.
7. Age ≥ 18 years old
8. ECOG performance status 0 or 1 within 56 days of start of chemoradiation.
9. Women of childbearing potential require a negative serum or urine pregnancy test
within 28 days prior to start of chemoradiation.
10. Written informed consent obtained from subject and ability for subject to comply with
the requirements of the study.
11. Adequate hematologic and renal function within 30 days of start of chemoradiation,
defined as:
- Hemoglobin ≥ 9.0 g/dL
- Platelets ≥ 100, 000 cells/mm3
- ANC ≥ 1.5 X 109/L
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase/alanine aminotransferase ≤ 3.0 x upper limit of normal
(ULN)
- Serum creatinine ≤1.5 x upper limit of normal (ULN) OR a calculated creatinine
clearance ≥60 mL/min
Exclusion Criteria:
1. AJCC 8th edition pT4 or cN3 disease.
2. Radiologic or clinical evidence of distant metastasis.
3. Recurrent disease.
4. Inability to achieve gross total resection at time of surgery.
5. Greater than 56 days (8 weeks) after surgical resection of the primary site.
6. Prior radiation to the head and neck > 30 Gy.
7. Prior active invasive (not in situ) malignancy within the prior 2 years, excluding
cutaneous basal cell or squamous cell carcinoma, low or intermediate risk prostate
cancer, papillary thyroid cancer, AJCC 8th edition stage I-II breast cancer, or low
grade non-Hodgkin lymphoma
8. 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
- Hepatic insufficiency resulting in clinical jaundice and/or known coagulation
defects
- Uncontrolled Acquired Immune Deficiency Syndrome (AIDS), defined as a CD4 count <
200 at screening or an AIDS-defining opportunistic infection within the last 6
months.
9. Moderate to severe hearing loss.
10. Active connective tissue disease (e.g. systemic lupus erythematous, scleroderma)
requiring immunosuppression.
11. Pregnant or breast-feeding women.
12. Prior allergic reaction to cisplatin.
13. Live vaccines within 30 days prior to the first dose of chemoradiation. Examples of
live vaccines include, but are not limited to, the following: measles, mumps, rubella,
chicken pox, yellow fever, rabies, BCG, and typhoid (oral vaccine). Season influenza
vaccines for injection are generally killed virus vaccines and are allowed; however
intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are
not allowed.
