Evaluation of De-escalated Adjuvant Radiation Therapy for Human Papillomavirus (HPV)-Associated Oropharynx Cancer

NCT02908477 | Completed Phase 3 Results DMC

• 2 other identifiers: 16-004083MC1675
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Oropharynx Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (6)

• Local/Regional Control

  2 years

• Quality of Life Between DART and Standard Adjuvant Therapy - FACT-HN

  1 year

• Quality of Life Between DART and Standard Adjuvant Therapy - EORTC-QLQ-HN35

  1 year

• Overall Survival

  2 years

• Disease-free Survival

  2 years

Study Arms (2)

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)

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)

Radiation: Adjuvant Radiation Therapy; Drug: Cisplatin

Interventions

Adjuvant Radiation Therapy RADIATION

60 Gy / 2 Gy fractions (standard arm) 30 - 36 Gy / 1.5 - 1.8 Gy b.i.d. fractions (experimental arm)

De-escalated Adjuvant Radiation Therapy; Standard of Care Treatment

Docetaxel DRUG

15 mg/m2. Experimental arm only.

Also known as: Taxotere

De-escalated Adjuvant Radiation Therapy

Cisplatin DRUG

40 mg/m2. Standard arm only.

Also known as: cisplatinum

Standard of Care Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Lymph node \> 3 cm
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (2)

• 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.

  PMID: 40907518 DERIVED

• Routman 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.

  PMID: 40402484 DERIVED

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Docetaxel; Cisplatin

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Katharine Price M.D.
• Organization: Mayo Clinic

Price.Katharine@mayo.edu

507-284-6139

Study Officials

• Daniel Ma, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2016
• First Posted: September 21, 2016
• Study Start: October 3, 2016
• Primary Completion: August 20, 2022
• Study Completion: November 15, 2024
• Last Updated: February 11, 2025
• Results First Posted: April 8, 2024

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)