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

Primary Purpose

Human Papillomavirus Infection, Stage I Oropharyngeal Squamous Cell Carcinoma, Stage II Oropharyngeal Squamous Cell Carcinoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Docetaxel

Hyperfractionation

Intensity-Modulated Radiation Therapy

Laboratory Biomarker Analysis

Quality-of-Life Assessment

About this trial

This is an interventional treatment trial for Human Papillomavirus Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Mayo Clinic in Arizona
Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (docetaxel, hyperfractionated IMRT)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

2-year Overall Survival (OS) Rate

The distribution of OS will be estimated using the method of Kaplan-Meier.

2-year Progression-free Survival (PFS)

The distribution of PFS will be estimated using the method of Kaplan-Meier.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT01932697

First Posted

August 27, 2013

Last Updated

September 18, 2023

Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT01932697

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

September 4, 2013 (Actual)

Primary Completion Date

October 20, 2016 (Actual)

Study Completion Date

December 28, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mayo Clinic

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

81 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (docetaxel, hyperfractionated IMRT)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

Hyperfractionation

Other Intervention Name(s)

Hyperfractionated Radiation, Hyperfractionated Radiation Therapy, superfractionated radiation therapy

Intervention Description

Undergo hyperfractionated IMRT

Intervention Type

Radiation

Intervention Name(s)

Intensity-Modulated Radiation Therapy

Other Intervention Name(s)

IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Intervention Description

Undergo hyperfractionated IMRT

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Other

Intervention Name(s)

Quality-of-Life Assessment

Other Intervention Name(s)

Quality of Life Assessment

Intervention Description

Ancillary studies

Primary Outcome Measure Information:

Title

2-year Loco-regional Tumor Control (LRC) Rate

Description

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.

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Incidence of Grade 3 or Higher Mucositis Oral

Description

Time Frame

4 months post-hyperfractionated radiation therapy

Title

2-year Overall Survival (OS) Rate

Description

The distribution of OS will be estimated using the method of Kaplan-Meier.

Time Frame

2 years

Title

2-year Progression-free Survival (PFS)

Description

The distribution of PFS will be estimated using the method of Kaplan-Meier.

Time Frame

From registration to the first of either disease recurrence or death, assessed up to 2 years

Title

2-year Distant Metastasis-free Survival Rate

Description

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.

Time Frame

2 years

Title

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.

Description

Time Frame

12 months

Title

Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (Version 4)

Description

Time Frame

1 year

Title

European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35)

Description

Time Frame

1 year post-treatment

Title

EuroQol Five-dimensional Instrument (EQ-5D-3L)

Description

Time Frame

1 year post-treatment

Other Pre-specified Outcome Measures:

Title

Changes in Transforming Growth Factor (TGF)-beta1 Levels

Description

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.

Time Frame

Baseline to 1 week post-radiation

Title

E6/E7 Messenger Ribonucleic Acid (mRNA) of HPV16, Assessed on a Chromogenic RNA in Situ Hybridization (ISH) Assay Called RNAscope

Description

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.

Time Frame

Baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel Ma

Organizational Affiliation

Mayo Clinic

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mayo Clinic in Arizona

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259

Country

United States

Facility Name

Mayo Clinic

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

31163012

Citation

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.

Results Reference

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

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