Circulating Tumor HPV DNA Driven Adjuvant Treatment Deintensification after Transoral Surgery for HPV-Positive Squamous Cell Carcinoma of the Oropharynx
Michael W. Sim, MD
Primary Investigator
Brief description of study
Detailed description of study
What will happen during the study?
This study is a prospective phase II trial, designed to assess the efficacy and feasibility of
adjuvant treatment deintensification guided by ctHPVDNA levels for patients with HPV+
OPSCC who undergo transoral surgery and neck dissection. Treatment under this protocol will
be offered to patients with early-stage disease, limited to T1-3, N0-2, M0 (AJCC 8th edition). The
assessments and interventions in this research study are experimental. There will be three
deintensification treatment options, with subjects being directed to a particular arm depending on
findings from ctHPVDNA testing and final pathology. Outcome measures will be compared to
historical data (OS of 81-84% 4 and LRC of 87% 28 ) for subjects who have been treated with
standard chemoradiation therapy or surgery with standard adjuvant therapy regimens, with the
potential goal of directly comparing deintensification to standard approaches in a subsequent
phase III trial. The target sample size is 120 evaluable subjects. The surgical treatment will be
performed by an experienced member of Indiana University (IU) Head and Neck Surgical
Oncology at University Hospital or IU North. Histopathologic analysis will be provided by the
IU Department of Pathology.
Subjects with undetectable postoperative ctHPVDNA levels and either N0 or N1 nodal disease
will be placed in the first arm of observation without further adjuvant treatment. Subjects with
undetectable postoperative ctHPVDNA levels and pathologic N2 nodal disease (five or more
positive nodes) will be placed in the second arm with deintensified radiation treatment of 30 gray. Finally, subjects with detectable postoperative ctHPVDNA will be placed in the third arm.
In the third arm, patients will undergo reimaging to evaluate for potentially operable disease,
followed by appropriate surgery as indicated. If surgery is performed, repeat ctHPVDNA levels
will be checked, and if then negative, patient will be placed in observation if N0 or N1 disease,
and 30 Gy of radiation if N2 disease on final pathologic staging. If repeat ctHPVDNA level is
positive, then patient will undergo 40 Gy of radiation. If the reimaging does not show obvious
operable disease, then patient will undergo 40 Gy of radiation.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Squamous Cell Carcinoma of Oropharynx, Throat Cancer, Tonsil Cancer
-
Age: 18 years - 100 years
-
Gender: All
Inclusion Criteria:
Pre-Surgery
• Subjects ≥ 18 years old at the time of informed consent.
• Ability to provide written informed consent and HIPAA authorization.
• Eastern Cooperative Oncology Group (ECOG) performance status 0–2 (refer to
Appendix).
• Primary tumor of the oropharynx (palatine tonsil, tongue base, soft palate, lateral or
posterior walls of oropharynx).
• Histopathologically confirmed squamous cell carcinoma.
• Detectable ctHPVDNA from blood samples collected prior to treatment.
• Resectable and accessible tumor with high probability of achieving negative margins.
• Smokers and non-smokers included.
• Tumor stage (AJCC 8th edition): T1 or T2, and select T3 tumors that are mobile and do
not invade the larynx.
• Nodal stage (AJCC 8th edition): N0, N1 or N2.
• Mobile neck nodes on physical exam if N positive.
• HPV+ tumor, as determined by p16, in-situ hybridization, real-time polymerase chain
reaction, or ctHPVDNA.
Post-Surgery
• Subjects with unknown primaries included if primary is definitively identified and
resectable with negative margins or if the palatine and lingual tonsils are thoroughly
resected and pathologically proven to be negative for a primary.
Exclusion Criteria:
• Serious medical condition preventing general anesthesia for surgery.
• History of previous head and neck radiation or previous head and neck cancer within
3 years.
• Distant metastatic disease present.
• Subjects with synchronous HPV+ oropharynx primaries
• Prior invasive malignant disease within 3 years, with the exception of non-melanoma skin
cancer and thyroid cancer, unless patient is deemed cured or disease free, in which case
patient may be included in the study.
• Lactating or pregnant women. Women of childbearing potential must have a negative
pregnancy test on the day of surgery. Women are considered to have childbearing potential (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) unless they meet one of the following criteria:
a. Has undergone a hysterectomy or bilateral oophorectomy; or
b. Has been naturally amenorrheic for at least 12 consecutive months.
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