Oropharynx CancerPhase 3NCT02908477
Evaluation of De-escalated Adjuvant Radiation Therapy for Human Papillomavirus (HPV)-Associated Oropharynx Cancer
A Phase 3 study testing Adjuvant Radiation Therapy, Docetaxel and Cisplatin in people with Oropharynx Cancer, run by Mayo Clinic at 2 sites in United States.
Trial summary
This study is designed for patients with a cancer of the oropharynx (tonsils or base of tongue) caused by the HPV virus. Traditional treatment involves surgery followed by six weeks of daily radiation therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oropharynx Cancer
- What is being tested?
- Adjuvant Radiation Therapy, Docetaxel and Cisplatin
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 228 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Oct 2016to 15 Nov 2024
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years.
- Histological confirmation of HPV+ squamous cell carcinoma of the oropharynx. HPV positivity will be defined as positive staining for p16 on immunohistochemistry (IHC).
- Gross total surgical resection with curative intent of the primary tumor and at least unilateral neck dissection within 7 weeks of registration.
- ECOG Performance Status (PS) 0 or 1
- Absence of distant metastases on standard diagnostic work-up ≤ 10 weeks prior to registration. (Chest CT, Chest x-ray (CXR), or PET/CT.)
- Must have one of the following risk factors:
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- Lymph node > 3 cm
- 2 or more positive lymph nodes
- Perineural invasion
- Lymphovascular space invasion
- T3 or T4 primary disease
- Lymph node extracapsular extension
- The following laboratory values obtained ≥14 days prior to registration.
- Absolute neutrophil count (ANC) ≥1500/mm3
- Platelet count ≥100,000/mm3
- Hemoglobin ≥8.0g/dL
- Creatinine ≤ 1.5 mg/dL or creatinine clearance ≥ 50 mL/min
- Total bilirubin < 2 x institutional upper limit of normal (ULN)
- AST or ALT < 3 x institutional ULN
- Negative pregnancy test done ≤7 days prior to registration, for women of childbearing potential only.
- Ability to complete questionnaire(s) by themselves or with assistance.
- Provide informed written consent.
- Willingness to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).
Who cannot join
- Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
- Immunocompromised patients and patients known to be HIV positive.
Show all 17Show fewer
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
- Other active malignancy ≤ 5 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history or prior malignancy, they must not be receiving other specific treatment for their cancer.
- Prior history of radiation therapy to the affected site.
- History of connective tissue disorders such as rheumatoid arthritis, lupus, or Sjogren's disease.
- Presence of any of the following risk factors after surgery:
- Any positive surgical margin.
- Adenopathy below the clavicles
- Prior systemic chemotherapy.
- Receiving any medications or substances which in the opinion of the investigators would interfere with treatment. Examples could include strong inhibitors of CYP3A4 at oncologist discretion (see Appendix IV).
- Severe pre-existing ototoxicity or neuropathy that would, in the opinion of the investigator, preclude the use of cisplatin chemotherapy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
About this study
Official title: DART-HPV: A Phase III Evaluation of De-escalated Adjuvant Radiation Therapy for HPV-Associated Oropharynx Cancer
This study is designed for patients with a cancer of the oropharynx (tonsils or base of tongue) caused by the HPV virus. Traditional treatment involves surgery followed by six weeks of daily radiation therapy. This study investigates a less intense radiation treatment following surgery that uses half the dose of radiation given over two weeks rather than six weeks. Patients will be randomly assigned to receive the less intense treatment versus the traditional treatment by coin flip. Patients are twice as likely to receive the less intense treatment during randomization.
Read the detailed description
Recent studies suggest that tumors in the oropharynx (tonsils or base of tongue) caused by the HPV virus are much more sensitive to radiation and chemotherapy. Standard treatment for HPV associated oropharynx tumor after surgery involves six weeks of radiation therapy and has many long term side effects and complications.
Mayo Clinic recently piloted a study investigating whether patients with HPV-associated oropharynx tumors can receive less radiation and chemotherapy after surgery when compared with the standard treatment. The investigators current study will compare the new, shorter treatment course (2 weeks of treatment) with the standard course of treatment (six weeks). Patients will be randomized to either the less intense or standard treatment arm. Patients will be twice as likely to receive the less intense treatment during randomization.
- Conditions
- Oropharynx Cancer
- Medical subject headings
- Oropharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adjuvant Radiation TherapyRadiation
60 Gy / 2 Gy fractions (standard arm) 30 - 36 Gy / 1.5 - 1.8 Gy b.i.d. fractions (experimental arm)
DocetaxelDrug
Also called Taxotere
15 mg/m2. Experimental arm only.
CisplatinDrug
Also called cisplatinum
40 mg/m2. Standard arm only.
| Study group | Role | What they receive |
|---|---|---|
| De-escalated Adjuvant Radiation Therapy | Experimental | Docetaxel 15 mg/m2 days 1, 8 + Radiation Therapy (RT) 30 Gy/1.5 Gy fractions twice daily (b.i.d.) days 1-12 only (intermediate risk) or 36 Gy/1.8 Gy b.i.d. fractions (high risk) Receives: Radiation: Adjuvant Radiation Therapy; Drug: Docetaxel |
| Standard of Care Treatment | Active comparator | RT 60 Gy/2 Gy fractions daily (qday) days 1-40. For high risk, add weekly Cisplatin 40 mg/m2 (Around days 1, 8, 15, 22, 29, 36) Receives: Radiation: Adjuvant Radiation Therapy; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade 3+ Adverse Events Rate
To compare rate of late grade 3-5 toxicities between de-escalated adjuvant radiation therapy (DART) and standard adjuvant therapy.
Measured: 2 years
Secondary outcomes (6)
Local/Regional Control
Local/regional failure percentage as assessed by imaging or physical exam at 2 years after study registration for patients treated with DART vs standard therapy.
Measured: 2 years
Quality of Life Between DART and Standard Adjuvant Therapy - FACT-HN
To compare the overall QOL between DART and standard adjuvant therapy at 1-year post-treatment as measured by the Functional Assessment of Cancer Therapy - Head \& Neck (FACT-HN) questionnaire. The FACT-HN consists of 12 questions related to symptoms and feeling over the past 7 days. Items are answered on a scale of 0-4 where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much.
Measured: 1 year
Quality of Life Between DART and Standard Adjuvant Therapy - EORTC-QLQ-HN35
To compare the overall QOL between DART and standard adjuvant therapy at 1-year post-treatment as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Head and Neck Module (EORTC-QLQ-HN35). The questionnaire consists of 35 items related to symptoms or problems during the past week. Thirty (30) items are answered on a scale of 0-4 where 0=not at all; 1=a little; 3=quite a bit, and 4=very much, and five (5) items are answered with yes/no.
Measured: 1 year
Overall Survival
Percentage of patients alive at 2 years.
Measured: 2 years
Disease-free Survival
Percentage of patients disease free and alive at 2 years.
Measured: 2 years
Distant Failure Associated With DART vs Standard Treatment
Distant failure is defined as cancer that has recurred or spread to a part of the body far away from the original tumor site
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2016 (estimated)
- Study start3 Oct 2016
- Primary completion20 Aug 2022
- Study completion15 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Oropharynx CancerStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 228 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel Ma, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02908477
- Sponsor's protocol ID
- 16-004083
- Other IDs
- MC1675
- Status last verified
- Jan 2025
- First submitted
- 26 Aug 2016
- Last updated
- 11 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Ma D, Price K, Moore E, Patel S, Hinni M, Routman D, Fruth B, Foster N, Van Abel K, Yin L, Neben-Wittich M, Garces Y, McGee L, Lester S, Rwigema JC, Holtzman A, Price D, Janus J, Kasperbauer J, Chintakuntlawar A, Garcia J, Foote R. De-escalated adjuvant radiotherapy versus standard adjuvant treatment for human papillomavirus-associated oropharyngeal squamous cell carcinoma (MC1675): a phase 3, open-label, randomised controlled trial. Lancet Oncol. 2025 Sep;26(9):1227-1239. doi: 10.1016/S1470-2045(25)00324-9.
PubMed 40907518Routman DM, Van Abel KM, Price KA, Moore EJ, Patel SH, Hinni ML, Fruth B, Foster NR, Yin LX, Neben-Wittich M, Garces YI, McGee LA, Lester SC, Gamez ME, Rwigema JM, Holtzman AL, Price DL, Janus JR, Kasperbauer JL, Chintakuntlawar AV, Garcia JJ, Foote RL, Ma DJ. ctDNA and Recurrence Risk for Adjuvant De-Escalation in HPV-Positive Oropharyngeal Carcinoma: A Secondary Analysis of the DART Phase 3 Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2025 Jul 1;151(7):665-672. doi: 10.1001/jamaoto.2025.0903.
PubMed 40402484
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DART-HPV: A Phase III Evaluation of De-escalated Adjuvant Radiation Therapy for HPV-Associated Oropharynx Cancer
- ClinicalTrials.gov ID
- NCT02908477
- Acronym / sponsor ID
- 16-004083
- Conditions
- Oropharynx Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 228 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 3 Oct 2016 (actual)
- Primary completion
- 20 Aug 2022 (actual)
- Study completion
- 15 Nov 2024 (actual)
- First posted
- 21 Sep 2016 (estimated)
- Results
- Posted 8 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed for patients with a cancer of the oropharynx (tonsils or base of tongue) caused by the HPV virus. Traditional treatment involves surgery followed by six weeks of daily radiation therapy. This study investigates a less intense radiation treatment following surgery that uses half the dose of radiation given over two weeks rather than six weeks. Patients will be randomly assigned to receive the less intense treatment versus the traditional treatment by coin flip. Patients are twice as likely to receive the less intense treatment during randomization.
Detailed description
Recent studies suggest that tumors in the oropharynx (tonsils or base of tongue) caused by the HPV virus are much more sensitive to radiation and chemotherapy. Standard treatment for HPV associated oropharynx tumor after surgery involves six weeks of radiation therapy and has many long term side effects and complications.
Mayo Clinic recently piloted a study investigating whether patients with HPV-associated oropharynx tumors can receive less radiation and chemotherapy after surgery when compared with the standard treatment. The investigators current study will compare the new, shorter treatment course (2 weeks of treatment) with the standard course of treatment (six weeks). Patients will be randomized to either the less intense or standard treatment arm. Patients will be twice as likely to receive the less intense treatment during randomization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| De-escalated Adjuvant Radiation Therapy | Experimental | Radiation: Adjuvant Radiation Therapy, Drug: DocetaxelDocetaxel 15 mg/m2 days 1, 8 + Radiation Therapy (RT) 30 Gy/1.5 Gy fractions twice daily (b.i.d.) days 1-12 only (intermediate risk) or 36 Gy/1.8 Gy b.i.d. fractions (high risk) |
| Standard of Care Treatment | Active comparator | Radiation: Adjuvant Radiation Therapy, Drug: CisplatinRT 60 Gy/2 Gy fractions daily (qday) days 1-40. For high risk, add weekly Cisplatin 40 mg/m2 (Around days 1, 8, 15, 22, 29, 36) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Age ≥ 18 years.
- Histological confirmation of HPV+ squamous cell carcinoma of the oropharynx. HPV positivity will be defined as positive staining for p16 on immunohistochemistry (IHC).
- Gross total surgical resection with curative intent of the primary tumor and at least unilateral neck dissection within 7 weeks of registration.
- ECOG Performance Status (PS) 0 or 1
- Absence of distant metastases on standard diagnostic work-up ≤ 10 weeks prior to registration. (Chest CT, Chest x-ray (CXR), or PET/CT.)
Key exclusion criteria (17 listed)
- Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
- Immunocompromised patients and patients known to be HIV positive.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adjuvant Radiation Therapy60 Gy / 2 Gy fractions (standard arm) 30 - 36 Gy / 1.5 - 1.8 Gy b.i.d. fractions (experimental arm) | Radiation | De-escalated Adjuvant Radiation Therapy, Standard of Care Treatment |
| DocetaxelAlso: Taxotere15 mg/m2. Experimental arm only. | Drug | De-escalated Adjuvant Radiation Therapy |
| CisplatinAlso: cisplatinum40 mg/m2. Standard arm only. | Drug | Standard of Care Treatment |
Primary outcome
Grade 3+ Adverse Events Rate
Time frame: 2 years
To compare rate of late grade 3-5 toxicities between de-escalated adjuvant radiation therapy (DART) and standard adjuvant therapy.
6 secondary outcomes
Local/Regional Control
Time frame: 2 years
Quality of Life Between DART and Standard Adjuvant Therapy - FACT-HN
Time frame: 1 year
Quality of Life Between DART and Standard Adjuvant Therapy - EORTC-QLQ-HN35
Time frame: 1 year
Overall Survival
Time frame: 2 years
Disease-free Survival
Time frame: 2 years
Distant Failure Associated With DART vs Standard Treatment
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40907518Ma D, Price K, Moore E, Patel S, Hinni M, Routman D, Fruth B, Foster N, Van Abel K, Yin L, Neben-Wittich M, Garces Y, McGee L, Lester S, Rwigema JC, Holtzman A, Price D, Janus J, Kasperbauer J, Chintakuntlawar A, Garcia J, Foote R. De-escalated adjuvant radiotherapy versus standard adjuvant treatment for human papillomavirus-associated oropharyngeal squamous cell carcinoma (MC1675): a phase 3, open-label, randomised controlled trial. Lancet Oncol. 2025 Sep;26(9):1227-1239. doi: 10.1016/S1470-2045(25)00324-9.
- Derived from this study: PubMed 40402484Routman DM, Van Abel KM, Price KA, Moore EJ, Patel SH, Hinni ML, Fruth B, Foster NR, Yin LX, Neben-Wittich M, Garces YI, McGee LA, Lester SC, Gamez ME, Rwigema JM, Holtzman AL, Price DL, Janus JR, Kasperbauer JL, Chintakuntlawar AV, Garcia JJ, Foote RL, Ma DJ. ctDNA and Recurrence Risk for Adjuvant De-Escalation in HPV-Positive Oropharyngeal Carcinoma: A Secondary Analysis of the DART Phase 3 Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2025 Jul 1;151(7):665-672. doi: 10.1001/jamaoto.2025.0903.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Ma, M.D. principal investigator
Mayo Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Adjuvant Radiation Therapy, Docetaxel and Cisplatin in people with Oropharynx Cancer, run by Mayo Clinic 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 23 inclusion and 17 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: finished, as of the sponsor's last update on 11 Feb 2025. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Grade 3+ Adverse Events Rate (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 NCT02908477, which also lists 2 linked publications.
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 11 Feb 2025.