Recruiting

Phase 2

CTDNAUsing CircuLating Tumor DNA to Risk Adapt Post-Operative Therapy for HPV-associated Oropharyngeal Cancer

Sponsor:

Zachary Zumsteg

Code:

NCT06445114

Conditions

Oropharyngeal Cancer

Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Cisplatin

Study Details

Brief summary:

This is a single institution phase II study that will enroll patients with T0-3N0-2 p16-positive oropharyngeal squamous cell carcinoma (OSCC) undergoing resection of all gross visible disease at the primary site and in the lymph nodes.

Conditions

Oropharyngeal Cancer

Carcinoma

Study ID

NCT06445114

Start date

May 12, 2025

Status verified date

Aug, 2026

Completion date

Jun, 2032

Anticipated

Primary completion date

Jun, 2032

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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.
For patients with pT0 tumors (unknown primary), there must be at least one metastatic lymph node present in cervical level II.
p16 is strongly positive by immunohistochemistry or high-risk HPV is detected by in-situ hybridization.
Have undergone or will undergo gross total resection of all known disease in the head and neck via transoral robotic surgery. For patients with clinical unknown primary tumors, a patient must undergo both ipsilateral tonsillectomy and base of tongue resection unless the primary is identified clinically or pathologically at the time of surgery. If the primary is identified, then only resection of the primary site is required. If the primary tumor is resected with negative margins with a non-robotic surgery, such as a diagnostic tonsillectomy, this is considered acceptable and further robotic surgery is not necessary.
Have undergone or will undergo neck dissection.
Have at least one of the following after surgery:

Pathologic stage T3
2 or more positive lymph nodes
At least one lymph node >3cm
Contralateral lymph node involvement
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.
Patients consented preoperatively are required to have detectable cTTMV-HPV DNA based on pre-operative NavDx testing. For patients consented post-operatively, NavDx testing should be performed on the tumor tissue to ensure detectable HPV DNA and for HPV subtyping.
Age ≥ 18 years old
ECOG performance status 0 or 2 within 56 days of start of chemoradiation.
Women of childbearing potential require a negative serum or urine pregnancy test within 28 days prior to start of chemoradiation.
Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
Adequate hematologic and renal function within 56 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 ≥50 mL/min estimated using the following Cockcroft-Gault equation

Exclusion Criteria:

AJCC 8th edition pT4 or cN3 disease.
Radiologic or clinical evidence of distant metastasis.
Recurrent disease.
Inability to achieve gross total resection at time of surgery.
Greater than 56 days (8 weeks) after surgical resection of the primary site.
Prior radiation to the head and neck > 30 Gy.
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, stage T1aN0 kidney cancer, low-grade T1-2N0 salivary cancer, AJCC 8th edition stage I-II breast cancer, well-differentiated neuroendocrine tumors (e.g., carcinoid tumors), low grade non-Hodgkin lymphoma, or Stage 0, I, and III cutaneous melanomas. Patients with synchronous or multifocal oropharyngeal cancers are not excluded, as long as at least one of these tumors meet inclusion criteria for the trial.
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 enrollment
Hepatic insufficiency resulting in clinical jaundice and/or known coagulation defects
Moderate to severe hearing loss.
Active connective tissue disease (e.g. systemic lupus erythematous, scleroderma) requiring immunosuppression.
Pregnant or breast-feeding women.
Prior allergic reaction to cisplatin.
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.

Study Design

Enrollment

50 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Single Arm

Low risk pathology with post-op HPV DNA (-): cisplatin-based chemoradiation with 30 Gy in 15 fractions and 3 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, and 15 of radiation.

Low risk pathology with post-op HPV DNA (+): cisplatin-based chemoradiation with 40 Gy in 20 fractions and 4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of radiation.

High risk pathology with post-op HPV DNA (-), excluding patients with both 5 LN+ and ENE+ or pre-op HPV DNA≤12 copies/mL: cisplatin-based radiation with 40 Gy in 20 fractions and 4 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, and 22 of radiation.

High risk pathology with post-op HPV DNA (+) OR pre-op HPV DNA≤12 copies/mL OR both 5 or more LN+ and ENE+: cisplatin-based radiation with 50 Gy in 25 fractions with 5 cycles of weekly cisplatin 40mg/m2 IV on Days 1, 8, 15, 22, and 29 of radiation.

Interventions

Cisplatin

Primary outcome measure

2-year progression-free (PFS) [ Time Frame: 2 Years ]

Central Contacts and Locations

Central contacts

Clinical Trial Navigator

310-423-5842 GroupCancerTrialInformation@cshs.org

Locations

Cedars-Sinai Cancer at Beverly Hills (THO)

Recruiting

Beverly Hills, California, United States, 90211

Cedars Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Contacts

Zachary S Zumsteg, MD

310-423-5842 zachary.zumsteg@cshs.org

Principal Investigator:

Zachary S Zumsteg, MD

CS Cancer at Valley Oncology Medical Group

Recruiting

Tarzana, California, United States, 91356

Contacts

Vanessa Vasco

Vanessa.Vasco@cshs.org

CS Cancer at the Hunt Cancer Center

Recruiting

Torrance, California, United States, 90505

Contacts

Sarah Valdez

310-750-3300 Sarah.Valdez@tmphysicians.com

More Information

Sponsor

Zachary Zumsteg

Last update posted

Aug 5, 2026

Last verified

Aug, 2026

Keywords

Transoral Robotic Surgery (TORS)
pT0 tumors (unknown primary)
p16

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Zachary Zumsteg on 2026-08-05.