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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
Results First Posted : September 18, 2019
Last Update Posted : September 18, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
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 Drug: Docetaxel Radiation: Hyperfractionation Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Evaluation of Adjuvant Hyperfractionated Radiation and Docetaxel for HPV Associated Oropharynx Cancer
Actual Study Start Date : September 2013
Actual Primary Completion Date : June 13, 2018
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 2-year Loco-regional Tumor Control (LRC) Rate [ Time Frame: Up to 2 years ]
    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 :
  1. Incidence of Grade 3 or Higher Mucositis Oral [ Time Frame: Up to 4 months post-hyperfractionated radiation therapy ]
    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.

  2. 2-year Overall Survival (OS) Rate [ Time Frame: From registration to death due to any cause, assessed up to 2 years ]
    The distribution of OS will be estimated using the method of Kaplan-Meier.

  3. 2-year Progression-free Survival (PFS) [ Time Frame: From registration to the first of either disease recurrence or death, assessed up to 2 years ]
    The distribution of PFS will be estimated using the method of Kaplan-Meier.

  4. 2-year Distant Metastasis-free Survival Rate [ Time Frame: Up to 2 years ]
    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.

  5. 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 ]
    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.

  6. 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 ]
    1 year post-treatment in QOL measured using the Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (version 4)

  7. 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 ]
    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)

  8. 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 ]
    1-year post-treatment QOL as measured by the three-level version of the EuroQol five-dimensional instrument (EQ-5D-3L)


Other Outcome Measures:
  1. 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.

  2. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01932697


Locations
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United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Daniel Ma Mayo Clinic
  Study Documents (Full-Text)

Documents provided by Mayo Clinic:

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Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01932697     History of Changes
Other Study ID Numbers: MC1273
NCI-2013-01652 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1273 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: August 30, 2013    Key Record Dates
Results First Posted: September 18, 2019
Last Update Posted: September 18, 2019
Last Verified: February 2019
Additional relevant MeSH terms:
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Papillomavirus Infections
Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action