Clinical Trials /

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

NCT02908477

Description:

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.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of De-escalated Adjuvant Radiation Therapy for Human Papillomavirus (HPV)-Associated Oropharynx Cancer
  • Official Title: DART-HPV: A Phase III Evaluation of De-escalated Adjuvant Radiation Therapy for HPV-Associated Oropharynx Cancer

Clinical Trial IDs

  • ORG STUDY ID: 16-004083
  • NCT ID: NCT02908477
  • NCT ALIAS: NCT03421470

Conditions

  • Oropharynx Cancer

Interventions

DrugSynonymsArms
DocetaxelTaxotereDe-escalated Adjuvant Radiation Therapy
CisplatincisplatinumStandard of Care Treatment

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
De-escalated Adjuvant Radiation TherapyExperimentalDocetaxel 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)
  • Docetaxel
Standard of Care TreatmentActive ComparatorRT 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)
  • Cisplatin

Eligibility Criteria

        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).

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events Rate
Time Frame:2 years
Safety Issue:
Description:To compare rate of late grade 3-5 toxicities between de-escalated adjuvant radiation therapy (DART) and standard adjuvant therapy.

Secondary Outcome Measures

Measure:Local/regional control
Time Frame:2 years
Safety Issue:
Description:Local/regional failure as assessed by imaging or physical exam at 2 years after study registration for patients treated with DART vs standard therapy.
Measure:Quality of Life
Time Frame:1 year
Safety Issue:
Description:To compare the overall QOL between DART and standard adjuvant therapy at 1-year post-treatment as measured by FACT H&N questionnaire.
Measure:Quality of Life
Time Frame:1 year
Safety Issue:
Description: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.
Measure:Overall Survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Disease-free survival
Time Frame:2 years
Safety Issue:
Description:
Measure:Distant failure associated with DART vs standard treatment
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mayo Clinic

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