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HPVPhase 2NCT05307939

A 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)

A Phase 2 study testing HPV ctDNA Assay, MRI Studies and EORTC QLQ H&N 35 and C30 in people with HPV and Oropharynx Cancer, run by Memorial Sloan Kettering Cancer Center at 8 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HPV, Oropharynx Cancer, HPV-Related Carcinoma
What is being tested?
HPV ctDNA Assay, MRI Studies and EORTC QLQ H&N 35 and C30
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
8 sitesUnited States
Study dates
24 Mar 2022to 24 Mar 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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.

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Acharf Shamseddine, MD contact

631-623-4272

shamseda@mskcc.org

Nancy Lee, MD contact

212-639-3341

leen2@MSKCC.ORG

8 sites in 1 country

United States8 sites, 8 recruiting

  • Memorial Sloan Kettering Basking Ridge (Limited protocol activities)

    Basking Ridge, New Jersey, 07920

    Achraf shamseddine, MD, 631-623-4272

    Recruiting

  • Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities)

    Commack, New York, 11725

    Achraf Shamseddine, MD, 631-623-4272

    Recruiting

  • Memorial Sloan Kettering Westchester (Limited Protocol Activites)

    East White Plains, New York, 10604

    Achraf Shamseddine, MD, 631-623-4272

    Recruiting

  • Baptist Alliance MCI (Data Collection Only)

    Miami, Florida, 33143

    Noah Kalman, MD, (786) 596-2000

    Recruiting

  • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

    Middletown, New Jersey, 07748

    Achraf Shamseddine, MD, 631-623-4272

    Recruiting

  • Memorial Sloan Kettering Bergen (Limited Protocol Activities)

    Montvale, New Jersey, 07645

    Achraf Shamseddine, MD, 631-623-4272

    Recruiting

  • Memorial Sloan Kettering Cancer Center (All Protocol Activities)

    New York, New York, 10065

    Achraf Shamseddine, MD, 631-623-4272

    Recruiting

  • Memorial Sloan Kettering Nassau (Limited protocol activities)

    Rockville Centre, New York, 11553

    Achraf Shamseddine, MD, 631-623-4272

    Recruiting

Other trials in United States

About this study

Official title: Phase II Trial Evaluating Selective Minimal Residual Disease Directed Adjuvant Radiation in Human Papilloma Virus Associated Oropharynx Carcinoma

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.

Being tested
HPV ctDNA Assay, MRI Studies, EORTC QLQ H&N 35 and C30, MDADI-HN, COST-FACIT
Keywords
ctDNA, NavDx test, 21-434, HPV-OPC, Memorial Sloan Kettering Cancer Center
Medical subject headings
Oropharyngeal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HPV ctDNA AssayDiagnostic test

    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 StudiesDiagnostic test

    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 C30Behavioural

    Also called The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module 35

    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-HNBehavioural

    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-FACITBehavioural

    Also called Comprehensive Score for financial Toxicity

    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)Radiation

    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)Combination product

    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

Study groups in NCT05307939
Study groupRoleWhat they receive
Screening, active surveillance, and treatment (Arm A)ExperimentalParticipants 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.
Receives: Diagnostic Test: HPV ctDNA Assay; Diagnostic Test: MRI Studies; Behavioral: EORTC QLQ H&N 35 and C30; Behavioral: MDADI-HN; Behavioral: COST-FACIT; Radiation: Intensity-Modulated Radiation Therapy (Arm A)
Screening and deescalated treatment (Arm B)ExperimentalParticipants 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.
Receives: Diagnostic Test: HPV ctDNA Assay; Diagnostic Test: MRI Studies; Behavioral: EORTC QLQ H&N 35 and C30; Behavioral: MDADI-HN; Behavioral: COST-FACIT; Combination Product: Chemoradiation (Arm B)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologically confirmed progression free survival

    To estimate pathologically confirmed progression free survival (pPFS) two years post-operatively in HPV associated OPC patients who undergo active surveillance.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2022
  2. Study start24 Mar 2022
  3. Primary completion24 Mar 2027 (estimated)
  4. Study completion24 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05307939
Sponsor's protocol ID
21-434
Status last verified
Apr 2026
First submitted
24 Mar 2022
Last updated
13 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing HPV ctDNA Assay, MRI Studies and EORTC QLQ H&N 35 and C30 in people with HPV and Oropharynx Cancer, run by Memorial Sloan Kettering Cancer Center at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Acharf Shamseddine, MD (631-623-4272, shamseda@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologically confirmed progression free survival (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05307939.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.

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