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

Human Papillomavirus Infection Clinical Trial

Official title:

Phase II Evaluation of Adjuvant Hyperfractionated Radiation and Docetaxel for HPV Associated Oropharynx Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01932697
• Other study ID #: MC1273
• Secondary ID: NCI-2013-01652MC
• Status: Completed
• Phase: Phase 2
• Start date: September 4, 2013
• Est. completion date: December 28, 2021

Study information

• Verified date: September 2023
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: December 28, 2021
• Est. primary completion date: October 20, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Human Papillomavirus Infection
• Papillomavirus Infections
• Squamous Cell Carcinoma of Head and Neck
• 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

Drug:
• Docetaxel
Given IV

Radiation:
• Hyperfractionation
Undergo hyperfractionated IMRT
• Intensity-Modulated Radiation Therapy
Undergo hyperfractionated IMRT

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in Transforming Growth Factor (TGF)-beta1 Levels	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.	Baseline to 1 week post-radiation
Other	E6/E7 Messenger Ribonucleic Acid (mRNA) of HPV16, Assessed on a Chromogenic RNA in Situ Hybridization (ISH) Assay Called RNAscope	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.	Baseline
Primary	2-year Loco-regional Tumor Control (LRC) Rate	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.	2 years
Secondary	Incidence of Grade 3 or Higher Mucositis Oral	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.	4 months post-hyperfractionated radiation therapy
Secondary	2-year Overall Survival (OS) Rate	The distribution of OS will be estimated using the method of Kaplan-Meier.	2 years
Secondary	2-year Progression-free Survival (PFS)	The distribution of PFS will be estimated using the method of Kaplan-Meier.	From registration to the first of either disease recurrence or death, assessed up to 2 years
Secondary	2-year Distant Metastasis-free Survival Rate	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.	2 years
Secondary	Change From Mean Baseline Score to Mean Score at 12 Months Post-RT in Swallow Function as Measured by the Pharyngeal Total Modified Barium Swallow Impairment Profile.	The swallow evaluation consists of a modified barium swallow study(MBS), Functional Oral Intake Scale(FOIS), and Performance Status Scale Head & Neck(PSS-HN).The 17 swallow questions are rated using a 0 to 5 point scale, with 0 meaning no impairment and 5 max impairment. 6 questions produce a total oral score; scores from 10 questions produce a total pharyngeal score; 1 question produces an esophageal score.The PAS is a validated 8-point scale that ranks the depth of the bolus entry into the airway.A score of 1 indicates no airway entrance;score of 6+ indicate bolus passage past the vocal folds (aspiration).FOIS ranges from 1(nothing by mouth) to 7(total oral diet with no restrictions).PSS-H&N has 3 components:eating in public(0=always eat alone to 100=no restriction), understandability of speech(0=never understandable, score 100=always understandable), and normalcy of diet(score 0=tube fed to 100=full diet).These scores are summed and normalized to a 0 to 100 scale where 100 is best.	12 months
Secondary	Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (Version 4)	The FACT-H&N is a multidimensional, self-report QOL instrument specifically designed for use with head and neck cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, in addition to 12 site specific items to assess for head and neck related symptoms. Each item is rated on a 0 to 4 type scale where 4 is favorable and 0 unfavorable, and then combined to produce subscale scores for each domain, as well as a global QOL score- with possible score range from 0 to 156. Higher scores represent better QOL.	1 year
Secondary	European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35)	QOL was measured by the European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35) at baseline and at 1-year post-treatment. Each question scores 0-4, with 0 being favorable and 4 being unfavorable. The average total score at baseline and average total score at 12 months post-RT is reported. The max total score possible is 140(Unfavorable) and the minimum total score possible is 0(Favorable). An increase in score indicates a greater quality of life A paired t-test compares the scores at these two timepoints.	1 year post-treatment
Secondary	EuroQol Five-dimensional Instrument (EQ-5D-3L)	QOL was measured by the three-level version of the EuroQol five-dimensional instrument (EQ-5D-3L) at baseline and 1-year post-treatment. This consisted of 5 questions, each score 0 to 3 points with 3 being unfavorable and 0 being favorable. The total possible score per patient per time point is 15 and a minimum score of 0(favorable). The change in average total score at baseline and 12 months post-RT is reported. A paired t-test compares the scores at these two time points. A higher score indicates greater impairment.	1 year post-treatment