Risk-adapted therapy in HPV+ oropharyngeal cancer using circulating tumor (ct)HPV DNA profile | The ReACT Study

This research is being conducted to understand if treatment can be tailored for
participants with HPV-related oropharynx cancers using both clinical features (stage of
the tumor, smoking status) combined with an investigational HPV blood test.

The names of the test and treatments involved in this study are:

- NavDx® HPV ctDNA testing (HPV blood test)

- Radiation therapy

- Chemotherapy: Cisplatin, or Carboplatin and Paclitaxel (not all participants receive
any or all of these agents)

Inclusion Criteria:

- Participants must meet the following eligibility criteria at the time of screening
to be eligible to participate in the study:

- Subject must have histologically or cytologically confirmed, stage I, II, or III (N3
disease excluded), HPV associated oropharyngeal (tongue base or tonsil) squamous
cell carcinoma, as defined by 2017 American Joint Committee on Cancer (AJCC), 8th
edition staging.

-- Patients with HPV-associated disease of unknown primary (cT0) are eligible

- HPV status should be confirmed on tissue biopsy or cytologic sample by any of the
following:

- Immunohistochemical staining for p16 with ≥70% expression

- Confirmatory DNA testing (PCR or ISH) for high-risk subtype

- Willing to provide blood and tissue from a diagnostic biopsy and blood samples
before, during, and after treatment.

- Detectable HPV ctDNA blood sample at baseline, prior to treatment, using the NavDx®
assay that detects HPV subtype 16

- Age 22 years or older

- ECOG performance status ≤ 2

- Participants should have adequate organ and marrow function if they are to receive
chemotherapy (cisplatin, or carboplatin and paclitaxel) with radiation concurrently
as determined by standard institutional guidelines and investigator preference
(parameters suggested below).

- absolute neutrophil count (ANC) ≥ 1000

- platelet count ≥ 100,000

- total bilirubin of 1.5 or less

- creatinine of 1.6 or less (or a CrCl ≥50 mL/min) per institutional standards.

- Planning to receive non-surgical management for HPV+ oropharyngeal cancer

- Ability to understand and the willingness to sign a written informed consent
document.

- Women of childbearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to
the start of (chemo)radiation therapy. "Women of childbearing potential (WOCBP)" is
defined as any female who has experienced menarche and who has not undergone
surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not
postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a
woman over 45 in the absence of other biological or physiological causes. In
addition, women under the age of 55 must have a documented serum follicle
stimulating hormone (FSH) level above 40 mIU/mL.

- Men who are sexually active with WOCBP must agree to use any contraceptive method
with a failure rate of less than 1% per year. Men who are sexually active with WOCBP
will be instructed to adhere to contraception for a period of 1 month after
treatment. Women who are not of childbearing potential (i.e., who are postmenopausal
or surgically sterile as well as azoospermic men) do not require contraception.

Exclusion Criteria:

- Patients with AJCC 2017 8th edition stage IVC (metastatic) disease; or patients with
fixed cervical nodal disease suggesting extranodal extension or N3 disease as
suggested by lymph nodes measuring >6 cm.

- Subject who has had prior radiation and/or chemotherapy for head and neck cancer.

- Any history of oncologic surgical resection (transoral robotic surgery, TORS) or
oncologic neck dissection prior to undergoing definitive RT or chemoradiation. Note:
prior tonsillectomy as part of identification of the primary tumor site or biopsy
and excisional nodal biopsy is/are acceptable provided the patient would be
standardly treated to definitive treatment doses of therapy off protocol. Patients
with HPV-associated unknown primary should not have undergone a neck dissection to
be eligible.

- Undetectable baseline HPV ctDNA result by NavDx® testing or detectable baseline HPV
ctDNA result for subtypes 18, 31, 33, or 35.

- Pregnant or lactating women.

- Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study
requirements.

- Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of
the skin that has undergone potentially curative therapy or in situ cervical cancer,
and low risk prostate adenocarcinoma being managed with active surveillance. A
history of another separate malignancy in remission without evidence of active
disease is permitted if chance3 of recurrence is thought to be low.