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

Phase 3

Active, not recruiting

• Conditions: Oropharynx Cancer
• Interventions: Radiation: Adjuvant Radiation Therapy; Drug: Docetaxel; Drug: Cisplatin

• Registration Number: NCT02908477
• Lead Sponsor: Mayo Clinic

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.

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 Timeline

• Study First Submitted: 2016-08-26
• Study First Submitted QC: 2016-09-16
• Study First Posted: 2016-09-21
• Study Start: 2016-10-03
• Primary Completion: 2022-08-20
• Results First Submitted: 2023-12-21
• Status Verified: 2024-04
• Results First Submitted QC: 2024-04-04
• Last Update Submitted: 2024-04-04
• Results First Posted: 2024-04-08
• Last Update Posted: 2024-04-08
• Study Completion: 2024-09-15

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

• 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
  • 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).

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Exclusion Criteria

• 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.

• 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
De-escalated Adjuvant Radiation Therapy	Adjuvant Radiation Therapy	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)
Standard of Care Treatment	Adjuvant Radiation Therapy	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)
De-escalated Adjuvant Radiation Therapy	Docetaxel	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)
Standard of Care Treatment	Cisplatin	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)

Primary Outcome Measures

Name	Time	Method
Grade 3+ Adverse Events Rate	2 years	To compare rate of late grade 3-5 toxicities between de-escalated adjuvant radiation therapy (DART) and standard adjuvant therapy.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	2 years	Percentage of patients alive at 2 years.
Local/Regional Control	2 years	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.
Quality of Life Between DART and Standard Adjuvant Therapy	1 year	To compare the overall QOL between DART and standard adjuvant therapy at 1-year post-treatment as measured by the EORTC H\&N quality of life questionnaire (QLQ) 35.
Disease-free Survival	2 years	Percentage of patients disease free and alive at 2 years.
Distant Failure Associated With DART vs Standard Treatment	2 years

Trial Locations

Locations (2)

Mayo Clinic in Arizona; 🇺🇸 Scottsdale, Arizona, United States

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States