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HPV-Associated Oropharyngeal Squamous Cell CarcinomaPhase 2NCT04900623

Risk-adapted Therapy in HPV+ Oropharyngeal Cancer Using Circulating Tumor (ct)HPV DNA Profile - The ReACT Study

A Phase 2 study testing NavDx HPV ctDNA Testing, Radiotherapy and Chemotherapy drug in people with HPV-Associated Oropharyngeal Squamous Cell Carcinoma and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Jonathan Schoenfeld, MD, MPH at 2 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 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. Read more about this study

Who is it for?
Ages 22 years and older
What is being tested?
NavDx HPV ctDNA Testing, Radiotherapy and Chemotherapy drug
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
2 sitesUnited States
Study dates
2 Jul 2021to 1 Jun 2032
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 22 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

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

Jonathan Schoenfeld, MD, MPH contact

617-632-3591

jonathan_schoenfeld@dfci.harvard.edu

United States2 sites, 2 recruiting

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

    Jonathan Schoenfeld, MD, MPH, 617.632.5296, jonathan_schoenfeld@dfci.harvard.edu

    Jonathan Schoenfeld, MD, MPH

    Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    Jonathan D. Schoenfeld, MD, MPH, 617.632.5296, jonathan_schoenfeld@dfci.harvard.edu

    Jonathan D. schoenfeld, MD

    Recruiting

Other trials in United States

About this 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)
Read the detailed description

This research study involves HPV DNA testing (a blood test that measures the levels of DNA from the human papillomavirus in the bloodstream which investigator think sheds from the cancer itself), radiation therapy, and chemotherapy for some participants.

The research study procedures includes: screening for eligibility, and study treatments including evaluations and follow-up visits.

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

  • NavDx® HPV ctDNA testing (HPV blood test)
  • Radiation therapy: Radiation therapy alone or combined with chemotherapy is considered a standard treatment for this disease. The investigators are researching the effectiveness of reducing the radiation doses and, in some cases, also reducing the chemotherapy dose for certain participants with favorable clinical characteristics and with certain HPV blood test results.
  • Chemotherapy: Cisplatin, or Carboplatin and Paclitaxel (not all participants receive any or all of these agents)
  • Study treatment will for up to 7 weeks and participants will be followed for 5 years from the beginning of the study.
  • It is expected that about 145 people will take part in this research study.

The HPV ctDNA levels will be measured using a blood test called NavDx®, which will be provided free of charge from the company NAVERIS. ctDNA testing refers to circulating tumor (ct)DNA or measuring DNA fragments floating in the bloodstream that are released from the cancer cells. This testing has shown promise in early detection of cancer recurrence in several solid tumor types (including colorectal, urothelial, and breast cancer). Additionally, recent studies have shown a connection between baseline ctDNA levels and disease risk.

The U.S. Food and Drug Administration (FDA) has not approved NavDx® as a method for guiding treatment decision-making, but this is an important part of this research study. While the NavDx® assay is investigational, it is performed in a Clinical Laboratory Improvement Amendment (CLIA) certified clinical laboratory and is currently available as a clinical tool for measuring HPV ctDNA levels in some cancer patients. CLIA regulations include federal standards applicable to all United States facilities or sites that test human specimens for health assessment or to diagnose, prevent, or treat disease

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. Radiation therapy alone or combined with chemotherapy is considered a standard treatment for this disease. The investigators are researching the effectiveness of reducing the radiation doses and, in some cases, also reducing the chemotherapy dose for certain participants with favorable clinical characteristics and with certain HPV blood test results.

Being tested
NavDx HPV ctDNA Testing, Radiotherapy, Chemotherapy drug
Keywords
HPV-Associated Oropharyngeal Squamous Cell Carcinoma, HPV Positive Oropharyngeal Squamous Cell Carcinoma, HPV-Mediated (P16-Positive) Oropharyngeal Carcinoma by AJCC V8 Pathologic Stage, HPV-Mediated (P16-Positive) Oropharyngeal Carcinoma by AJCC V8 Clinical Stage, Pathologic Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Medical subject headings
Oropharyngeal Neoplasms

What participants receive

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

  • NavDx HPV ctDNA TestingDevice

    Also called NavDx

    Blood will be collected and shared with an outside lab for analysis. This test will be done at Week 4 and at End of Treatment. This test will be done at at End of Treatment and in follow-up at 3, 6, 9, and 12 months after completing the study treatment. In years 2 and 3 after treatment, the test will be collected every 6 months or twice a year. The specimens will be identifiable. The specimens will be banked for future use.

  • RadiotherapyRadiation

    Also called Intensity-modulated radiotherapy (IMRT), Proton beam radiotherapy

    Radiation Therapy (administered daily, Monday-Friday). Higher risk participants will receive standard radiation dose for up to 7-8 weeks. Lower risk participants will receive a lower dose and treatment will only last 5-6 weeks.

  • Chemotherapy drugDrug

    Also called Bolus Cisplatin, Cisplatin, Carboplatin with Paclitaxel

    Chemotherapy and radiation therapy are both considered standard treatments

    • Bolus Cisplatin: Infused every 21 days for up to 2 or 3 doses.
    • Weekly Cisplatin or Carboplatin with Paclitaxel: Infused weekly during radiation therapy.
Study groups in NCT04900623
Study groupRoleWhat they receive
LOW RISK RT (ALONE OR WITH SOC CHEMOExperimentalThe research study procedures include: screening for eligibility, and study treatments including evaluations and follow-up visits * NavDx HPV ctDNA Testing: Blood will be collected and shared with an outside lab for analysis (less than 10 mL of blood or about 2 teaspoons). The results of this test will determine what radiation dose received . The specimens will be de-identified. The specimens will be banked for future use. * Radiation Therapy: Lower risk participants will receive a lower dose and treatment will only last 5-6 weeks. * Chemotherapy: Chemotherapy and radiation therapy are both considered standard treatments for your type of cancer. The study doctor will decide whether or not chemotherapy with radiation and the type of chemotherapy. * Bolus Cisplatin: Infused every 21 days for up to 2 or 3 doses. * Weekly Cisplatin or Carboplatin with Paclitaxel: Infused weekly during radiation therapy
Receives: Device: NavDx HPV ctDNA Testing; Radiation: Radiotherapy; Drug: Chemotherapy drug
INTERMEDIATE RISK RT (ALONE OR WITH SOC CHEMOExperimentalThe research study procedures include: screening for eligibility, and study treatments including evaluations and follow-up visits * NavDx HPV ctDNA Testing: Blood will be collected and shared with an outside lab for analysis (less than 10 mL of blood or about 2 teaspoons). The results of this test will determine what dose of radiation received. The specimens will be de-identified. The specimens will be banked for future use. * Radiation Therapy: Higher risk participants will receive standard radiation dose for up to 7-8 weeks * Chemotherapy: Chemotherapy and radiation therapy are both considered standard treatments for your type of cancer. The study doctor will decide whether or not chemotherapy with radiation and the type of chemotherapy. * Bolus Cisplatin: Infused every 21 days for up to 2 or 3 doses. * Weekly Cisplatin or Carboplatin with Paclitaxel: Infused weekly during radiation therapy
Receives: Device: NavDx HPV ctDNA Testing; Radiation: Radiotherapy; Drug: Chemotherapy drug

What is being measured

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

  1. Progression Free Survival 2 Years

    Progression-free survival (PFS) is defined as the time from the date of study registration to first invasive local, regional, distant progression, or death due to any cause. Participants alive without progression are censored at date of last disease evaluation

    Measured: 2 Years

Secondary outcomes (5)

  1. Overall Survival at 2 Years

    Defined as the time from study registration to death due to any cause, or censored at date last known alive.

    Measured: 2 Years

  2. Rate of Distant Failure

    Distant metastatic-free survival (DMFS) is defined as the time from confirmed disease response (CR/PR) to the earlier of the first occurrence of distant or metastatic disease, or death due to any cause. Participants alive without distant or metastatic progression are censored at date of last disease evaluation.

    Measured: every 12 weeks (or 3 months) from the time of therapy completion for years 1 and 2, and every 24 weeks (or 6 months) from the time of therapy completion in year 3.

  3. Best Overall Response

    The best response recorded from the start of the treatment until disease progression or recurrence, with documentation of local (primary site) or regional (neck lymph node) disease clearance being of interest. Clinical or radiographic evidence of progressive locoregional disease beyond 12 weeks (or 3 months) from the end of treatment should be documented and ideally confirmed by locoregional or distant disease biopsy, neck dissection, or salvage surgery. CT or MRI (of head and neck region, with chest CT), or PET-CT may be used as radiographic evaluation of overall disease status.

    Measured: every 12 weeks (or 3 months) from the time of therapy completion for years 1 and 2, and every 24 weeks (or 6 months) from the time of therapy completion in year 3.

  4. Score Change FACT-H&N survey data

    The self-administered Functional Assessment of Cancer Therapy - Head \& Neck Cancer (FACT-HN) questionnaire consists of FACT-G, a cancer specific QOL questionnaire that includes 27 questions in 4 domains - physical, social, emotional, and function, and a 12-time H\&N cancer-specific modules. Each item is rated on a 0 to 4 scale. Higher scores represent better Quality of Life. A clinically significant change in score on this instrument is represented by an increase of 6 units or decrease of 12 units

    Measured: baseline up to 5 years

  5. Safety and Toxicity

    Evaluated by measuring feeding tube rate.

    Measured: 6 and 12 months after protocol therapy

Timeline

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

  1. First posted25 May 2021
  2. Study start2 Jul 2021
  3. Primary completion1 Jun 2030 (estimated)
  4. Study completion1 Jun 2032 (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
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
145 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04900623
Sponsor's protocol ID
21-191
Status last verified
Aug 2026
First submitted
19 May 2021
Last updated
5 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to Sponsor Investigator or designee. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Publications

  • Hanna GJ, Gupta TR, Trippa L, Rettig EM, Margalit DN, Tishler RB, Pashtan I, Kim E, Droznin A, Gunasti L, Maddox R, Minken J, Mukundan D, Sehgal K, Dennis MJ, O'Connor T, Qian JM, Boyd GH, Saraf A, Massiel Gil D, Sethi RK, Annino DJ, Goguen LA, Guenette JP, Bakhtiar M, Jo VY, Wong K, Uppaluri R, Haddad RI, Schoenfeld JD. Risk-adapted therapy guided by human papillomavirus (HPV) circulating tumor DNA in HPV-positive oropharyngeal cancer (ReACT 1.0): an exploratory phase II trial. Nat Commun. 2026 May 7;17(1):6142. doi: 10.1038/s41467-026-72984-7.

    PubMed 42098120

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NavDx HPV ctDNA Testing, Radiotherapy and Chemotherapy drug in people with HPV-Associated Oropharyngeal Squamous Cell Carcinoma and HPV Positive Oropharyngeal Squamous Cell Carcinoma, run by Jonathan Schoenfeld, MD, MPH at 2 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 19 inclusion and 7 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 5 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 Jonathan Schoenfeld, MD, MPH (617-632-3591, jonathan_schoenfeld@dfci.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival 2 Years (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 NCT04900623, which also lists 1 linked publication.

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 5 Aug 2026.

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