Clinical Trials /

Radiation Therapy and Docetaxel in Treating Patients With HPV-Related Oropharyngeal Cancer

NCT01932697

Description:

This phase II trial studies how well radiation therapy and docetaxel work in treating patients with human papillomavirus (HPV)-related oropharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving radiation therapy with docetaxel my kill more tumor cells.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Radiation Therapy and Docetaxel in Treating Patients With HPV-Related Oropharyngeal Cancer
  • Official Title: Phase II Evaluation of Adjuvant Hyperfractionated Radiation and Docetaxel for HPV Associated Oropharynx Cancer

Clinical Trial IDs

  • ORG STUDY ID: MC1273
  • SECONDARY ID: NCI-2013-01652
  • SECONDARY ID: MC1273
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT01932697

Conditions

  • Human Papillomavirus Infection
  • Stage I Oropharyngeal Squamous Cell Carcinoma
  • Stage II Oropharyngeal Squamous Cell Carcinoma
  • Stage III Oropharyngeal Squamous Cell Carcinoma
  • Stage IVA Oropharyngeal Squamous Cell Carcinoma
  • Stage IVB Oropharyngeal Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
DocetaxelDocecad, RP56976, Taxotere, Taxotere Injection ConcentrateTreatment (docetaxel, hyperfractionated IMRT)

Purpose

This phase II trial studies how well radiation therapy and docetaxel work in treating patients with human papillomavirus (HPV)-related oropharyngeal cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving radiation therapy with docetaxel my kill more tumor cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the cumulative incidence of local/regional failure at 2 years after study
      registration.

      SECONDARY OBJECTIVES:

      I. To characterize the rate of acute grade 3 or higher functional mucosal adverse events (up
      to 1 month post-radiation therapy [XRT]) associated with adjuvant docetaxel +
      hyperfractionated radiotherapy (key secondary endpoint).

      II. To assess changes in overall survival, disease-free survival, distant failure rates, and
      quality of life (QOL) associated with adjuvant docetaxel and hyperfractionated radiation.

      III. To characterize other acute adverse events (up to 1 month post-XRT) and late grade 3 or
      higher non-hematologic adverse events (up to 2 years post-XRT) associated with adjuvant
      docetaxel + hyperfractionated radiotherapy.

      TERTIARY OBJECTIVES:

      I. To determine the genetic alterations of oropharynx tumor specimens and the detection rate
      of corresponding cell-free deoxyribonucleic acid (cfDNA) in the pre-surgical, post-surgical,
      and post-radiation blood of oropharynx cancer patients.

      OUTLINE:

      Patients receive docetaxel intravenously (IV) over 1 hour on days 1 and 8 and undergo
      hyperfractionated intensity-modulated radiation therapy (IMRT) twice daily (BID) 5 days a
      week on days 1-12 for a total of 20 fractions.

      After completion of study treatment, patients are followed up at 14 days, 1 month, every 3
      months for 2 years, every 6 months for 1 year and then annually for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (docetaxel, hyperfractionated IMRT)ExperimentalPatients receive docetaxel IV over 1 hour on days 1 and 8 and undergo hyperfractionated IMRT BID 5 days a week on days 1-12 for a total of 20 fractions.
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  PRE-REGISTRATION

          -  Provide written informed consent

          -  Submission of research blood draw to be stored until after surgical resection of the
             primary tumor and confirmation of human papilloma virus (HPV) positivity (Mayo Clinic
             Rochester patients only)

          -  Patients with oropharynx carcinoma with a smoking history of ˂ 10 pack-year or
             equivalent 10 year history of tobacco product use and no recent history (within last 5
             years) of tobacco use

          -  REGISTRATION

          -  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

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Smoking history < 10 pack years or equivalent 10 year history of tobacco product use

          -  Absence of distant metastases on standard diagnostic work-up =< 10 weeks prior to
             registration; (chest computed tomography [CT], chest x-ray [CXR], positron emission
             tomography [PET]/CT, etc.)

          -  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 microscopic T4a primary disease

               -  Lymph node extracapsular extension

          -  Absolute neutrophil count (ANC) >= 1500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Hemoglobin >= 9.0 g/dL

          -  Direct bilirubin within upper limit of normal (ULN)

          -  Creatinine =< ULN x 1.5

          -  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 significant tobacco history within the past five years

          -  Any of the following:

               -  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 human immunodeficiency virus (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

          -  History of myocardial infarction =< 180 days prior to registration, or congestive
             heart failure requiring use of ongoing maintenance therapy for life-threatening
             ventricular arrhythmias

          -  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 for the study cancer; NOTE: prior chemotherapy for a
             different cancer is allowable

          -  History of allergic reaction to docetaxel

          -  Receiving any medications or substances that are strong or moderate inhibitors of
             cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)

               -  Use of strong or moderate inhibitors is prohibited =< 7 days prior to
                  registration

          -  Receiving any medications or substances that are inducers of CYP3A4

               -  Use of inducers is prohibited =< 12 days prior to registration
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:2-year Loco-regional Tumor Control (LRC) Rate
Time Frame:Up to 2 years
Safety Issue:
Description:The 2-year loco-regional tumor control (LRC) rate (percentage) is defined as the percentage of patients with no local/regional recurrence or death 2 years after study registration.

Secondary Outcome Measures

Measure:Incidence of Grade 3 or Higher Mucositis Oral
Time Frame:Up to 4 months post-hyperfractionated radiation therapy
Safety Issue:
Description:The overall percentage of patients experiencing grade 3 or higher mucositis oral graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 are reported below.
Measure:2-year Overall Survival (OS) Rate
Time Frame:From registration to death due to any cause, assessed up to 2 years
Safety Issue:
Description:The distribution of OS will be estimated using the method of Kaplan-Meier.
Measure:2-year Progression-free Survival (PFS)
Time Frame:From registration to the first of either disease recurrence or death, assessed up to 2 years
Safety Issue:
Description:The distribution of PFS will be estimated using the method of Kaplan-Meier.
Measure:2-year Distant Metastasis-free Survival Rate
Time Frame:Up to 2 years
Safety Issue:
Description:The 2-year Distant metastasis-free survival rate (percentage) is defined as the percentage of patients with no distant recurrence or death 2 years after study registration.
Measure:Change From Baseline to 12 Months Post-RT in Swallow Function as Measured by the Pharyngeal Total Modified Barium Swallow Impairment Profile
Time Frame:Baseline to up to 12 months post-treatment
Safety Issue:
Description:Swallowing will be scored (yes, no) for aspiration, penetration, velopharyngeal incompetence, epiglottic inversion, tongue base retraction, and pharyngeal swallow response using the metric outlined by Eisbruch et al.
Measure:1 Year Post-treatment in QOL Measured Using the Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (Version 4)
Time Frame:1 year post-treatment
Safety Issue:
Description:1 year post-treatment in QOL measured using the Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (version 4)
Measure:1-year Post-treatment QOL as Measured by the European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35)
Time Frame:1 year post-treatment
Safety Issue:
Description:1-year post-treatment QOL as measured by the European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35)
Measure:1-year Post-treatment QOL as Measured by the Three-level Version of the EuroQol Five-dimensional Instrument (EQ-5D-3L)
Time Frame:1 year post-treatment
Safety Issue:
Description:1-year post-treatment QOL as measured by the three-level version of the EuroQol five-dimensional instrument (EQ-5D-3L)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Mayo Clinic

Last Updated

April 8, 2020