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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01932697
First received: August 27, 2013
Last updated: May 28, 2014
Last verified: May 2014
  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 or by stopping them from dividing. Giving radiation therapy with docetaxel my kill more tumor cells.


Condition Intervention Phase
Human Papilloma Virus Infection
Stage I Squamous Cell Carcinoma of the Oropharynx
Stage II Squamous Cell Carcinoma of the Oropharynx
Stage III Squamous Cell Carcinoma of the Oropharynx
Stage IVA Squamous Cell Carcinoma of the Oropharynx
Stage IVB Squamous Cell Carcinoma of the Oropharynx
Tongue Cancer
Drug: docetaxel
Radiation: intensity-modulated radiation therapy
Radiation: hyperfractionated radiation therapy
Procedure: quality-of-life assessment
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Evaluation of Adjuvant Hyperfractionated Radiation and Docetaxel for HPV Associated Oropharynx Cancer

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Cumulative incidence of local/regional failure [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Overall survival (OS) [ Time Frame: From registration to death due to any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    The distribution of DFS will be estimated using the method of Kaplan-Meier.

  • Distant failure rates [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • E6/E7 messenger ribonucleic acid (mRNA) of HPV16, assessed on a chromogenic RNA in situ hybridization (ISH) assay called RNAscope [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 80
Study Start Date: September 2013
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (docetaxel, hyperfractionated IMRT)
Patients receive docetaxel IV over 1 hour on days 1 and 8 and undergo hyperfractionated IMRT BID on days 1-5 and 8-12 (20 fractions).
Drug: docetaxel
Given IV
Other Names:
  • RP 56976
  • Taxotere
  • TXT
Radiation: intensity-modulated radiation therapy
Undergo hyperfractionated IMRT
Other Name: IMRT
Radiation: hyperfractionated radiation therapy
Undergo hyperfractionated IMRT
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies

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.

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) on days 1-5 and 8-12 (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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 =< 8 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01932697

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Daniel J. Ma    507-284-2511    ma.daniel@mayo.edu   
Principal Investigator: Daniel J. Ma         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Daniel Ma Mayo Clinic
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01932697     History of Changes
Other Study ID Numbers: MC1273, NCI-2013-01652, 12-005272, MC1273, P30CA015083
Study First Received: August 27, 2013
Last Updated: May 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Papillomavirus Infections
Carcinoma
Carcinoma, Squamous Cell
Papilloma
Virus Diseases
Tongue Neoplasms
Oropharyngeal Neoplasms
Warts
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Mouth Diseases
Stomatognathic Diseases
Tongue Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Pharyngeal Diseases
Otorhinolaryngologic Diseases
DNA Virus Infections
Skin Diseases, Viral
Tumor Virus Infections
Skin Diseases, Infectious
Skin Diseases
Docetaxel
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014