Blood-Based Biomarkers to Inform Treatment and Radiation Therapy Decisions for HPV Associated Oropharyngeal Squamous Cell Head and Neck Cancers
Oropharyngeal Human Papillomavirus-Positive Squamous Cell Carcinoma, Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
About this trial
This is an interventional treatment trial for Oropharyngeal Human Papillomavirus-Positive Squamous Cell Carcinoma
Eligibility Criteria
Inclusion Criteria:
- PRE-REGISTRATION (optional): Provide written informed consent
- Age >= 18 years
- Histological confirmation of p16+ OPSCC or HPV(+) OPSCC
- Plan for gross total surgical resection via trans oral surgery with curative intent and at least unilateral neck dissection OR chemoradiotherapy with cisplatin
- Absence of distant metastases on standard diagnostic work-up =< 16 weeks prior to registration. (Chest CT or PET/CT)
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) =< 1
- Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
- Ability to complete questionnaire(s) by themselves or with assistance
- Provide written informed consent
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
- Willing to provide blood samples for correlative research purposes, including anonymous shipment of samples to for NavDx testing
Exclusion Criteria:
Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)+
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
- Other active malignancy =< 5 years prior to registration. EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or prostate or localized endometrioid endometrial cancer. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer
- Prior history of radiation therapy to the affected site
- Prior systemic chemotherapy in the last 5 years
- History of connective tissue disorders such as rheumatoid arthritis, lupus, or Sjogren's disease
- History of allergic reaction to docetaxel
- Receiving any medications or substances which in the opinion of the investigators would interfere with treatment. Examples could include strong inhibitors of cytochrome P450 3A4 (CYP3A4) at oncologist discretion
- Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the investigator, preclude the use of cisplatin chemotherapy
cT4 primary tumor
- NOTE: Patients with no intermediate risk factors after surgery, low risk patients, as defined by T1, T2, tumors with lymph node less than 3cm, no intermediate or high risk factors such as lymphatic invasion (LVSI), ENE, perineural invasion (PNI), positive margin, will go off study and be observed per current clinical standard of care
- Patients found to have HPV non 16 type, or HPV detectability in blood less than <50 tumor tissue modified viral (TTMV) will not be candidates for de-escalation in Groups 1 and 2 and will be treated in Group 3. They will receive 60 Gy +/- cisplatin. If treated primarily with chemoradiation (chemoRT) (Group 4), these patients will not be candidates for de-escalation but can remain on study receiving 70 Gy with all corresponding correlative studies applying
- Patients with unknown (radiologic/clinically occult) primaries but p16+ or HPV+ neck adenopathy can be registered to go on study. Should after primary resection, no primary tumor be identified, the patient will go off study and be treated per institutional standard of care
- All treatment primarily, including surgery and chemotherapy will be performed at the enrolling institution
Sites / Locations
- Mayo Clinic in ArizonaRecruiting
- Mayo Clinic in Florida
- Mayo Clinic in RochesterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Active Comparator
Experimental
Experimental
Experimental
Group 1 (observation)
Group 2 (DART, docetaxel)
Group 3 (IMRT/IMPT, with/without cisplatin)
Group 4 (IMRT/IMPT, cisplatin)
Patients undergo observation following standard of care surgery. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 months follow-up. Patients also undergo CT, PET/CT, or magnetic MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months.
Patients undergo DART with/without mucosal sparing BID on days 1-12 Monday-Friday for a total of 20 fractions within 8 weeks of standard of care surgery. Patients receive concurrent docetaxel IV over 1 hour on days 1 and 8 (Mondays preferred). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months.
Patients undergo IMRT or IMPT QD on days 1-40 Monday-Friday for a total of 30 fractions within 6 weeks of standard of care surgery. Depending on risk status, patients may also receive concurrent cisplatin IV over 1-2 hours once a week QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS at pre-op, 2 weeks post-op, and 3 and 12 months post-treatment. Patients also undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing at pre-op, 1-2 days post-op, 2 weeks post-op, end of RT, and 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months.
Patients undergo IMRT or IMPT therapy QD on days 1-40 Monday-Friday for 28 or 35 fractions based on biomarker response along with concurrent cisplatin IV over 1-2 hours QW on Monday, Tuesday, or Wednesday or once every 3 weeks for 6 doses (or accepted alternate regimen when drug shortage applies per physician discretion). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo MBSS prior to RT and at 3 and 12 months post RT. Patients undergo CT, PET/CT, or MRI at baseline and 3 months and 1, 2 and 5 years post treatment. Patients undergo blood specimen collection for NavDx testing pre-RT, 4 weeks into RT, anticipated fraction 20, end of RT, 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, 48, and 60 months.