Recruiting

Phase 2

ctDNA TestingA Study on Using Cell-Free Tumor DNA (ctDNA) Testing to Decide When to StartRoutine Treatment in People With Human Papilloma Virus (HPV)- Associated Oropharynx Cancer (OPC)

Sponsor:

Memorial Sloan Kettering Cancer Center

Code:

NCT05307939

Conditions

HPV

Oropharynx Cancer

HPV-Related Carcinoma

HPV-Related Malignancy

HPV Positive Oropharyngeal Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

HPV ctDNA Assay

MRI Studies

EORTC QLQ H&N 35 and C30

MDADI-HN

COST-FACIT

Study Details

Brief summary:

This study will look at whether monitoring HPV ctDNA levels is an effective way to detect cancer relapse risk in people with HPV-OPC. All participants will have recently had surgery to treat their disease, or they will be scheduled to have this surgery.

In Arm A the researchers will see whether monitoring participants' HPV ctDNA levels can safely identify patients who do not need radiation therapy (RT) after surgery and whose RT can be delayed until their HPV ctDNA levels become detectable.

In Arm B, the researchers will see whether patients who usually need 6-6.5 weeks of CRT can be selected by HPV ctDNA to receive 3 weeks of CRT.

Conditions

HPV

Oropharynx Cancer

HPV-Related Carcinoma

HPV-Related Malignancy

HPV Positive Oropharyngeal Squamous Cell Carcinoma

Study ID

NCT05307939

Start date

Mar 24, 2022

Status verified date

Apr, 2026

Completion date

Mar 24, 2027

Anticipated

Primary completion date

Mar 24, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Age ≥ 18
ECOG 0-2
HPV-16 squamous cell carcinoma of the oropharynx or HPV-16 head and neck squamous cell carcinoma of unknown primary . HPV status must be confirmed by in-situ hybridization.
HPV ctDNA detectable by HPV digital PCR (Naveris assay) with a minimum of 50 copies/mL pre-operatively.
Surgical resection of all gross disease with no gross disease visualized on post-operative imaging.

o For patients with pT0 (unknown primary) evaluation for the primary should include PET/CT, direct laryngoscopy, ipsilateral tonsillectomy, and targeted biopsy. This should be followed by a neck dissection.

Two, undetectable (<1 copy/mL) post-operative HPV ctDNA within 2-6 weeks following surgery (blood drawn at least one week apart preferred).
A minimum of one of the following pathologic criteria: (Arm A)

AJCC 7 Stage: pT0N1-N2b, pT1N1, pT2N1, or ≥pT3
AJCC 7 ≥pN2
Lymphovascular invasion
Perineural invasion
Close pathologic margin (≤ 3 mm)
Signed informed consent form by the participant or their legally authorized representative (LAR).
A minimum of one of the following pathologic criteria (Arm B):

Microscopic positive margin
Extracapsular extension
Signed informed consent form by the participant or their legally authorized representative (LAR).

Additional criteria for Arm B only:

Adequate hematologic function within 30 days prior to registration, defined as follows:

White Blood Count (WBC) ≥ 2 K/mcL
Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
Platelets ≥ 100,000 cells/mm3
Hemoglobin ≥ 8.0 g/dl; Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable
Adequate renal function within 30 days prior to registration, defined as follows:

Serum creatinine < 1.5 mg/dl or creatinine clearance (CC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula:
CCr male = \[(140 - age) x (wt in kg)\] divided by \[(Serum Cr mg/dl) x (72)\]
CCr female = 0.85 x (CrCl male)
Adequate hepatic function within 30 days prior to registration, defined as follows:

\- Bilirubin < 2 mg/dl o AST or ALT < 3 x the upper limit of normal

Negative serum pregnancy test within 14 days prior to registration for women of childbearing potential

Exclusion Criteria:

Metastatic disease
Non-HPV16 genotype (i.e. HPV-18,-31, -33, -35)
Patients who receive surgery at outside institution. Exceptions can be made for high-volume surgical centers at the discretion of the PI/co-PI
Prior head and neck radiation
Patients without pre-operative HPV ctDNA or pre-operative HPV ctDNA ≤ 50 copies/mL
Subjects with simultaneous primary cancers outside of the oropharynx

o Note: Exceptions can be made for patients with simultaneous primaries outside of the oropharynx if determined by the PI/Co-PI, then the patient can proceed with protocol activities

Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for 3 years or if cure rate from treatment at 5 years is 90% or greater

o Note: Exceptions can be made for patients with prior invasive malignancy if determined by the PI/Co-PI, then the patient can proceed with protocol activities

Prior systemic chemotherapy for the study cancer

o Note: prior chemotherapy for a different cancer is allowable

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
Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization within 30 days of registration
Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
Lack of ability to understand and willingness to sign a written informed consent and complete questionnaires.

Study Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Diagnostic

Interventions and Outcome Measures

Arms

experimental: Screening, active surveillance, and treatment (Arm A)

Participants who meet criteria for the treatment phase (a post-operative HPV ctDNA which rose from initial undetectable to meet HPV16 ctDNA criteria and have no clinical or radiographic evidence of gross disease) will undergo delayed standard of care adjuvant radiation (50-60 Gy administered in 1.8-2 Gy fractions) based on the patient's initial pathology. Treatment will be initiated within 4 weeks of a NavDx result. Subjects will undergo FDG PET/CT simulation and standard radiation treatment planning and this FDG PET/CT will also be utilized to rule out distant metastases. Diagnostic FDG PET/CT fusion is also allowed for treatment planning and to rule out distant metastases. Non-therapeutic assessments will be completed.

experimental: Screening and deescalated treatment (Arm B)

Participants who meet criteria for the de-escalated treatment phase (Arm B) will undergo adjuvant radiation (30 Gy administered in 2 Gy fractions) with concurrent chemotherapy.

They will undergo FDG PET/CT simulation and standard radiation treatment planning and this FDG PET/CT will also be utilized to rule out distant metastases. Diagnostic FDG PET/CT fusion is also allowed for treatment planning and to rule out distant metastases. Non-therapeutic assessments will be completed and the Study calendar.

Interventions

HPV ctDNA Assay

HPV ctDNA evaluation will be completed using NavDx which is a validated digital droplet PCR (ddPCR) assay that targets primers and hydrolysis probes to specifically detect amplicons within the E6 and E7 genes encoded by high-risk HPV strain 16, and the E7 gene for high-risk HPV strains: 18, 31, 33, and 35.

MRI Studies

Research MRI studies will be acquired at Memorial Sloan Kettering using a fast multi-phase spoiled gradient echo sequence. A Gadolinium-based agent will be used for DCE-MRI studies.

EORTC QLQ H&N 35 and C30

The EORTC QLQ H\&N 35 s a validated 35-item site specific assessment tool. The module uses 7 multi-item scales to measure problems with swallowing, senses, speech, social eating and social contact. In addition, 11 single-item scales are utilized in assessing problems with teeth, mouth opening, dry mouth, sticky saliva, coughing, feeling ill, as well as use of analgesics, nutritional supplements, feeding tube and finally, weight gain and weight loss. All of the scales and single item measures range in score from 0 to 100. High scores for the Global Health Status/QoL scale represent high QoL, high scores for the functional scales represent high/healthy levels of functioning, but high scores for the symptom scales/items represent high levels of symptomatology/problems. Scoring the two instruments yields a total of 33 distinct scores and we will examine all of these scored.

MDADI-HN

The MDADI-HN is a questionnaire scored on a scale of 1 to 5, consisting of global, emotional, functional, and physical subscales. The MDADI-HN evaluates the effects of dysphagia on QOL.

COST-FACIT

Comprehensive Score for financial Toxicity or COST survey is a validated screening tool to assess objective and subjective questions about treatment-related financial distress. It is scored from 0-44, where lower composite scores reflect greater risk of financial toxicity.

Intensity-Modulated Radiation Therapy (Arm A)

59.4-60 Gy in 1.8-2 Gy fractions: CTV\_primary, Involved/Adjacent to nodal levels. 50 Gy to this volume is allowed as per MSK institutional standards in patients with clear or close margins and 2-4 involved nodes. 45-50.4 Gy in 1.8-2 Gy fractions: Dissected node positive neck: uninvolved levels that are not adjacent to positive node - Dissected node negative neck

Chemoradiation (Arm B)

30 Gy in 2 Gy fractions: CTV\_primary, CTV\_node-positive neck, CTV\_node-negative neck, received de-escalated postoperative chemoradiation. Adjuvant radiation will be administered as previously outlined. Concurrent chemotherapy will be administered as per standard of care. Cisplatin will be administered concurrently with radiation. For non-cisplatin candidates, carboplatin/5fu will be administered. Reasons for using carboplatin/5FU instead of cisplatin need to be charted in the medical record, but the decision belongs to the treating physician. Cisplatin may be given up to 3 days before the scheduled dates, if necessary for medical or personal reasons

Primary outcome measure

Pathologically confirmed progression free survival [ Time Frame: 2 years ]

Central Contacts and Locations

Central contacts

Acharf Shamseddine, MD

631-623-4272 shamseda@mskcc.org

Nancy Lee, MD

212-639-3341 leen2@MSKCC.ORG

Locations

Baptist Alliance MCI (Data Collection Only)

Recruiting

Miami, Florida, United States, 33143

Contacts

Noah Kalman, MD

(786) 596-2000

Memorial Sloan Kettering Basking Ridge (Limited protocol activities)

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Achraf shamseddine, MD

631-623-4272

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Achraf Shamseddine, MD

631-623-4272

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Achraf Shamseddine, MD

631-623-4272

Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)

Recruiting

Commack, New York, United States, 11725

Contacts

Achraf Shamseddine, MD

631-623-4272

Memorial Sloan Kettering Westchester (Limited Protocol Activites)

Recruiting

East White Plains, New York, United States, 10604

Contacts

Achraf Shamseddine, MD

631-623-4272

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

Recruiting

New York, New York, United States, 10065

Contacts

Achraf Shamseddine, MD

631-623-4272

Memorial Sloan Kettering Nassau (Limited protocol activities)

Recruiting

Rockville Centre, New York, United States, 11553

Contacts

Achraf Shamseddine, MD

631-623-4272

More Information

Sponsor

Memorial Sloan Kettering Cancer Center

Last update posted

Apr 13, 2026

Last verified

Apr, 2026

Keywords

ctDNA
NavDx test
21-434
HPV-OPC
Memorial Sloan Kettering Cancer Center

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center on 2026-04-13.