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

• ClinicalTrials.gov Identifier: NCT01932697
• Recruitment Status: Unknown
• First Posted: August 30, 2013
• Results First Posted: September 18, 2019
• Last Update Posted: April 8, 2020
• Sponsor: Mayo Clinic
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Mayo Clinic

Study Description

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 81 participants
• Allocation: N/A
• 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 4, 2013
• Actual Primary Completion Date: October 20, 2016
• Estimated Study Completion Date: December 30, 2020

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Locations

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

• Principal Investigator: Daniel Ma; Mayo Clinic

  Study Documents (Full-Text)

Documents provided by Mayo Clinic:

Study Protocol and Statistical Analysis Plan  [PDF] November 8, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ma DJ, Price KA, Moore EJ, Patel SH, Hinni ML, Garcia JJ, Graner DE, Foster NR, Ginos B, Neben-Wittich M, Garces YI, Chintakuntlawar AV, Price DL, Olsen KD, Van Abel KM, Kasperbauer JL, Janus JR, Waddle M, Miller R, Shiraishi S, Foote RL. Phase II Evaluation of Aggressive Dose De-Escalation for Adjuvant Chemoradiotherapy in Human Papillomavirus-Associated Oropharynx Squamous Cell Carcinoma. J Clin Oncol. 2019 Aug 1;37(22):1909-1918. doi: 10.1200/JCO.19.00463. Epub 2019 Jun 4. Erratum In: J Clin Oncol. 2020 Apr 1;38(10):1118.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01932697
• 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
• Results First Posted: September 18, 2019
• Last Update Posted: April 8, 2020
• Last Verified: March 2020

Additional relevant MeSH terms:

Papillomavirus Infections; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms; Neoplasms by Site; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Docetaxel; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action