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

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ClinicalTrials.gov Identifier: NCT01932697
Recruitment Status : Active, not recruiting
First Posted : August 30, 2013
Last Update Posted : February 19, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Tracking Information
First Submitted Date  ICMJE August 27, 2013
First Posted Date  ICMJE August 30, 2013
Last Update Posted Date February 19, 2019
Actual Study Start Date  ICMJE September 2013
Actual Primary Completion Date June 13, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2014)
Cumulative incidence of local/regional failure [ Time Frame: Up to 2 years ]
The 2-year cumulative incidence of local/regional failure will be estimated by the competing risk method, where the competing risks are distant failures and deaths from other causes (i.e. deaths from distant failure or non-oropharynx cancer).
Original Primary Outcome Measures  ICMJE
 (submitted: August 27, 2013)
2-year cumulative incidence of local/regional failure [ Time Frame: Up to 2 years ]
The 2-year cumulative incidence of local/regional failure will be estimated by the competing risk method, where the competing risks are distant failures and deaths from other causes (i.e. deaths from distant failure or non-oropharynx cancer).
Change History Complete list of historical versions of study NCT01932697 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2016)
  • Change in QOL measured using the Xerostomia- Related Quality of Life Scale (XeQOLS) form, European Quality of Life (EuroQol) 5D (Eq-5D), Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (version 4), and Dermatology Life Quality Index [ Time Frame: Baseline to up to 24 months post-treatment ]
    QOL scores will be explored descriptively. In addition, differences between post-baseline and baseline QOL scores will be analyzed using a paired-sample t-test or the nonparametric equivalent to see if the QOL tends to improve over time with treatment.
  • Change in swallowing studies [ Time Frame: Baseline to up to 12 months post-treatment ]
    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. The swallowing questions will be explored descriptively to detect patterns and substantial changes over time. In addition, McNemar's test for paired samples will be used to see if the swallowing questions significantly change over time for each post-baseline time point.
  • Disease-free survival (DFS) [ Time Frame: From registration to the first of either disease recurrence or death, assessed up to 5 years ]
    The distribution of DFS will be estimated using the method of Kaplan-Meier.
  • Distant failure rates [ Time Frame: Up to 2 years ]
    The 2-year cumulative incidence of distant failure will be estimated by the competing risk method, where the competing risks are local/regional failures and deaths from other causes (i.e. deaths from local/regional failure or non-oropharynx cancer).
  • Incidence of acute adverse events graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 1 month post-XRT ]
    The maximum grade for each type of acute adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns, especially focusing on grade 3+ adverse events, regardless of attribution to the study treatment.
  • Incidence of acute grade 3 or higher functional mucosal adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 1 month post-hyperfractionated radiation therapy ]
  • Incidence of late adverse events graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 2 years post-treatment ]
    The maximum grade for each type of adverse event will be recorded for each patient for up to 2 years post-treatment, and frequency tables will be reviewed to determine patterns, especially focusing on grade 3+ non-hematologic adverse events, regardless of attribution to the study treatment.
  • Overall survival (OS) [ Time Frame: From registration to death due to any cause, assessed up to 5 years ]
    The distribution of OS will be estimated using the method of Kaplan-Meier.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2013)
  • Incidence of acute grade 3 or higher functional mucosal adverse events graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 1 month post-hyperfractionated radiation therapy ]
  • Overall survival (OS) [ Time Frame: From registration to death due to any cause, assessed up to 5 years ]
    The distribution of OS will be estimated using the method of Kaplan-Meier.
  • Disease-free survival (DFS) [ Time Frame: From registration to the first of either disease recurrence or death, assessed up to 5 years ]
    The distribution of DFS will be estimated using the method of Kaplan-Meier.
  • Distant failure rates [ Time Frame: Up to 2 years ]
    The 2-year cumulative incidence of distant failure will be estimated by the competing risk method, where the competing risks are local/regional failures and deaths from other causes (i.e. deaths from local/regional failure or non-oropharynx cancer).
  • Change in QOL measured using the Xerostomia- Related Quality of Life Scale (XeQOLS) form, European Quality of Life (EuroQol) 5D (Eq-5D), Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (version 4), and Dermatology Life Quality Index [ Time Frame: Baseline to up to 24 months post-treatment ]
  • Change in swallowing studies [ Time Frame: Baseline to up to 12 months post-treatment ]
    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. The swallowing questions will be explored descriptively to detect patterns and substantial changes over time. In addition, McNemar's test for paired samples will be used to see if the swallowing questions significantly change over time for each post-baseline time point.
  • Incidence of acute adverse events graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 1 month post-XRT ]
    The maximum grade for each type of acute adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns, especially focusing on grade 3+ adverse events, regardless of attribution to the study treatment.
  • Incidence of late adverse events graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 2 years post-treatment ]
    The maximum grade for each type of adverse event will be recorded for each patient for up to 2 years post-treatment, and frequency tables will be reviewed to determine patterns, especially focusing on grade 3+ non-hematologic adverse events, regardless of attribution to the study treatment.
Current Other Outcome Measures  ICMJE
 (submitted: February 23, 2016)
  • Changes in transforming growth factor (TGF)-beta1 levels [ Time Frame: Baseline to 1 week post-radiation ]
    These markers will be correlated with clinical endpoints like acute adverse events, cumulative incidence rates of local/regional failure, overall survival, and disease-free survival.
  • E6/E7 messenger ribonucleic acid (mRNA) of HPV16, assessed on a chromogenic RNA in situ hybridization (ISH) assay called RNAscope [ Time Frame: Baseline ]
    These markers will be correlated with clinical endpoints like acute adverse events, cumulative incidence rates of local/regional failure, overall survival, and disease-free survival.
Original Other Outcome Measures  ICMJE
 (submitted: August 27, 2013)
  • E6/E7 messenger ribonucleic acid (mRNA) of HPV16, assessed on a chromogenic RNA in situ hybridization (ISH) assay called RNAscope [ Time Frame: Baseline ]
    These markers will be correlated with clinical endpoints like acute adverse events, cumulative incidence rates of local/regional failure, overall survival, and disease-free survival.
  • Changes in transforming growth factor (TGF)-beta1 levels [ Time Frame: Baseline to 1 week post-radiation ]
    These markers will be correlated with clinical endpoints like acute adverse events, cumulative incidence rates of local/regional failure, overall survival, and disease-free survival.
 
Descriptive Information
Brief Title  ICMJE Radiation Therapy and Docetaxel in Treating Patients With HPV-Related Oropharyngeal Cancer
Official Title  ICMJE Phase II Evaluation of Adjuvant Hyperfractionated Radiation and Docetaxel for HPV Associated Oropharynx Cancer
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Docetaxel
    Given IV
    Other Names:
    • Docecad
    • RP56976
    • Taxotere
    • Taxotere Injection Concentrate
  • Radiation: Hyperfractionation
    Undergo hyperfractionated IMRT
    Other Names:
    • Hyperfractionated Radiation
    • Hyperfractionated Radiation Therapy
    • superfractionated radiation therapy
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo hyperfractionated IMRT
    Other Names:
    • IMRT
    • Intensity Modulated RT
    • Intensity-Modulated Radiotherapy
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
Study Arms Experimental: Treatment (docetaxel, hyperfractionated IMRT)
Patients 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.
Interventions:
  • Drug: Docetaxel
  • Radiation: Hyperfractionation
  • Radiation: Intensity-Modulated Radiation Therapy
  • Other: Laboratory Biomarker Analysis
  • Other: Quality-of-Life Assessment
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 20, 2016)
81
Original Estimated Enrollment  ICMJE
 (submitted: August 27, 2013)
40
Estimated Study Completion Date October 2019
Actual Primary Completion Date June 13, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01932697
Other Study ID Numbers  ICMJE MC1273
NCI-2013-01652 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1273 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Daniel Ma Mayo Clinic
PRS Account Mayo Clinic
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP