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Phase II Treatment Stratification Trial Using Neck Dissection-Driven Selection to Improve Quality of Life for Low Risk Patients With HPV+ Oropharyngeal Squamous Cell Cancer

Primary Purpose

Oropharyngeal Squamous Cell Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Neck Dissection
Standard-of-Care (SOC) Transoral Surgery of Primary Site
SOC Radiation
SOC Carboplatin
SOC Paclitaxel
Videofluoroscopy
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oropharyngeal Squamous Cell Cancer focused on measuring head and neck neoplasms, HPV, human papilloma virus, de-escalation, low-risk, oropharyngeal cancer

Eligibility Criteria

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

Inclusion Criteria:

  • Patients must have pathologically-confirmed, previously untreated, p16-positive oropharyngeal squamous cell carcinoma
  • Patients must have pretreatment neck and chest imaging
  • Tumors must be potentially surgically resectable via a transoral approach, at the discretion of the treating surgeon
  • Patients with T stage T1-3
  • Patients with N stage N0-N2c
  • ECOG (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.) Performance status 0-2
  • Patients are adults (Age >18)
  • Patients must agree to biospecimen submission for tissue and serum processing and storage for secondary biomarker studies
  • Patients must give documented informed consent to participate in this study.
  • Patients must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of chemoradiation (treatment) and for 3 months after discontinuing treatment. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to starting treatment.
  • Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 30 days after study treatment. Women not of childbearing potential will be defined as all women older than age 50 and anovulatory for 12 months.
  • Sexually active males must use a condom during intercourse while receiving chemoradiation and for 90 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Likewise, male subjects should not donate sperm during the time they are receiving chemoradiation and for 90 days after stopping treatment.

Exclusion Criteria:

  • Prior head and neck radiation or prior chemotherapy for HNSCC (Head and Neck Squamous Cell Carcinoma)
  • Patients with T4 disease
  • Patients with N3 disease
  • FNA evidence of squamous cell carcinoma involving 3 or more lymph nodes
  • Patients with matted lymph nodes, defined as three nodes abutting one another with loss of intervening fat plane that is a replaced with radiologic evidence of extracapsular spread
  • Patients with an outside primary site biopsy showing perineural or perivascular invasion
  • Documented evidence of distant metastases.
  • Active infection
  • Patients residing in prison.
  • Age < 18 years
  • Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • Unstable angina or a history of myocardial ischemia within prior 6 months

  • Patients with any of the following laboratory values at baseline:

    • Absolute neutrophil count (ANC) < 1,000/mm3
    • Platelets < 75,000/mm3
    • Hemoglobin < 9.0 gm/dL
    • Calculated or measured creatinine clearance (method determined by the prescribing physicians) < 50 ml/min
    • Bilirubin > 1.5 x ULN (Upper Limit of Normal), except for patients with known Gilbert syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN
    • Aspartate transaminase (AST) > 3.0 x ULN
    • Alanine transaminase (ALT) > 3.0 x ULN
  • Pregnancy or breastfeeding female.
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation

Sites / Locations

  • University of Michigan Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Neck Dissection

Arm Description

Patients undergo up-front neck dissection of the cervical lymph nodes to determine stratification into one of three standard-of-care treatment groups: transoral surgery of the primary site, radiation or chemoradiation.

Outcomes

Primary Outcome Measures

Median Change in Quality of Life (QOL) From Baseline to 12 Months Post Treatment
Four QOL instruments will be administered: the University of Washington Quality of Life (UWQOL), University of Michigan Head and Neck Quality of Life Instrument (HN-QOL), the University of Michigan Voice Related Quality of Life Measure (V-RQOL), and the FACT Head and Neck (version 4) (FACT H&N). Results of each of the 4 surveys will be reported in separate rows in the results table. The difference in scores from baseline to 12 months after completion of study treatment is calculated for each participant, with the median across all participants reported for each survey. Higher scores indicate better QOLs. Range for Questionnaires: HN QOLs: -100 to +100 VR QOLs: -100 to +100 UW QOLs: -100 to +100 FACTHN Physical: -28 to +28 FACTHN Social: -28 to +28 FACTHN Emotional: -24 to +24 FACTHN Functional: -28 to +28 FACTHN subscale: -40 to +40 FACTHN Total: -148 to +148

Secondary Outcome Measures

Impact of Neck Dissection on Shoulder Function Using the Neck Dissection Impairment Index
The neck dissection impairment index will be scored and summarized for all patients who receive neck dissection. Scores ranging from 0-100 with higher scores indicating better function
Median Change in Quality of Life (QOL) From Baseline to 24 Months Post Treatment
Four QOL instruments will be administered: the University of Washington Quality of Life (UWQOL), University of Michigan Head and Neck Quality of Life Instrument (HN-QOL), the University of Michigan Voice Related Quality of Life Measure (V-RQOL), and the FACT Head and Neck (version 4) (FACT H&N). Results of each of the 4 surveys will be reported in separate rows in the results table. The difference in scores from baseline to 24 months after completion of study treatment is calculated for each participant, with the median across all participants reported for each survey. Higher scores indicate better QOLs. Range for Questionnaires: HN QOLs: -100 to +100 VR QOLs: -100 to +100 UW QOLs: -100 to +100 FACTHN Physical: -28 to +28 FACTHN Social: -28 to +28 FACTHN Emotional: -24 to +24 FACTHN Functional: -28 to +28 FACTHN subscale: -40 to +40 FACTHN Total: -148 to +148
Disease Specific Survival (DSS)
Proportion of patients alive at 3 years from date of neck dissection. Death from OPSCC (Oropharyngeal Squamous Cell Cancer) will be considered an event for DSS. Death from other causes will be censored at time of death.
Progression Free Survival (PFS)
Proportion of patients alive and free of disease persistence, progression or recurrence at 3 years from the date of completion of study treatment. Persistent disease at completion of treatment, post-treatment recurrence or disease specific death will be defined events for progression free survival (PFS).
Overall Survival (OS)
Proportion of patients alive at 3 years from date of neck dissection. Death from any cause will be considered an event for overall survival.

Full Information

First Posted
May 24, 2016
Last Updated
June 1, 2023
Sponsor
University of Michigan Rogel Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT02784288
Brief Title
Phase II Treatment Stratification Trial Using Neck Dissection-Driven Selection to Improve Quality of Life for Low Risk Patients With HPV+ Oropharyngeal Squamous Cell Cancer
Official Title
Phase II Treatment Stratification Trial Using Neck Dissection-Driven Selection to Improve Quality of Life for Low Risk Patients With HPV+ Oropharyngeal Squamous Cell Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
October 31, 2016 (Actual)
Primary Completion Date
July 10, 2020 (Actual)
Study Completion Date
July 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Investigators will determine whether a treatment paradigm of up-front neck dissection, to more accurately pathologically stage patients, minimizing the number of treatment modalities in patients with low risk oropharyngeal squamous cell carcinoma, can improve quality of life.
Detailed Description
After enrollment, all patients will undergo neck dissection and primary site biopsy. Pathology will be reviewed, and patients will proceed into one of three standard-of-care (SOC) treatment groups. The treatments themselves are not the focus of this study; the focus of this study is quality of life in this population, after a pathology-based treatment plan, to assess the utility of the investigational "neck dissection first" paradigm. The SOC treatment plans are as follows: Patients with a single lymph node that measures less than six centimeters, have no extracapsular extension in the lymph node, and have no perineural or perivascular invasion of the primary biopsy will undergo transoral surgery of the primary site. Patients who have 2 positive nodes with no extracapsular extension, or have perineural or perivascular invasion of the primary biopsy will undergo radiation. Patients who have extracapsular extension in any number of lymph nodes or in those patients in whom negative margins are unable to be obtained after the completion of transoral surgery will undergo chemoradiation. After completion of therapy (surgical, radiation, or combined modality) patients will be followed closely on an outpatient basis including regular exams, quality of life questionnaires, and interval surveillance imaging as clinically indicated. Swallowing function will also be addressed by videofluoroscopy one year after completion of therapy. Blood/plasma and oral rinses for correlative studies will be collected at 3-month intervals during 3 years of follow up. This study was initially registered as if it were an inter-group comparison; however, the original and consistent intent has been to determine whether a treatment paradigm of neck dissection guided staging as a whole can minimize the number of standard treatment methods used, leading to improved quality of life in low risk patients with HPV+ oropharyngeal squamous cell cancer. Though certain groups are expected to need multimodal definitive treatment downstream of the experimental "neck dissection first" paradigm, the population must be assessed as one group in this trial to assess the utility of the paradigm.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oropharyngeal Squamous Cell Cancer
Keywords
head and neck neoplasms, HPV, human papilloma virus, de-escalation, low-risk, oropharyngeal cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Neck Dissection
Arm Type
Experimental
Arm Description
Patients undergo up-front neck dissection of the cervical lymph nodes to determine stratification into one of three standard-of-care treatment groups: transoral surgery of the primary site, radiation or chemoradiation.
Intervention Type
Procedure
Intervention Name(s)
Neck Dissection
Intervention Description
All patients will undergo neck dissection of the cervical lymph nodes
Intervention Type
Procedure
Intervention Name(s)
Standard-of-Care (SOC) Transoral Surgery of Primary Site
Intervention Description
Patients with a single lymph node that measures less than six centimeters, have no extracapsular extension in the lymph node, and have no perineural or perivascular invasion of the primary biopsy will undergo transoral surgery of the primary site.
Intervention Type
Radiation
Intervention Name(s)
SOC Radiation
Intervention Description
Patients who have 2 positive nodes with no extracapsular extension, or have perineural or perivascular invasion of the primary biopsy will undergo radiation.
Intervention Type
Drug
Intervention Name(s)
SOC Carboplatin
Intervention Description
Patients who have extracapsular extension in any number of lymph nodes or in those patients in whom negative margins are unable to be obtained after the completion of transoral surgery will undergo chemoradiation (Radiation, Carboplatin and Paclitaxel).
Intervention Type
Drug
Intervention Name(s)
SOC Paclitaxel
Intervention Description
Patients who have extracapsular extension in any number of lymph nodes or in those patients in whom negative margins are unable to be obtained after the completion of transoral surgery will undergo chemoradiation (Radiation, Carboplatin and Paclitaxel).
Intervention Type
Procedure
Intervention Name(s)
Videofluoroscopy
Intervention Description
All patients undergo a videofluoroscopy procedure one year after completion of therapy to assess swallowing function.
Primary Outcome Measure Information:
Title
Median Change in Quality of Life (QOL) From Baseline to 12 Months Post Treatment
Description
Four QOL instruments will be administered: the University of Washington Quality of Life (UWQOL), University of Michigan Head and Neck Quality of Life Instrument (HN-QOL), the University of Michigan Voice Related Quality of Life Measure (V-RQOL), and the FACT Head and Neck (version 4) (FACT H&N). Results of each of the 4 surveys will be reported in separate rows in the results table. The difference in scores from baseline to 12 months after completion of study treatment is calculated for each participant, with the median across all participants reported for each survey. Higher scores indicate better QOLs. Range for Questionnaires: HN QOLs: -100 to +100 VR QOLs: -100 to +100 UW QOLs: -100 to +100 FACTHN Physical: -28 to +28 FACTHN Social: -28 to +28 FACTHN Emotional: -24 to +24 FACTHN Functional: -28 to +28 FACTHN subscale: -40 to +40 FACTHN Total: -148 to +148
Time Frame
Baseline to 12 Months post-treatment (up to approximately 15 months post neck dissection).
Secondary Outcome Measure Information:
Title
Impact of Neck Dissection on Shoulder Function Using the Neck Dissection Impairment Index
Description
The neck dissection impairment index will be scored and summarized for all patients who receive neck dissection. Scores ranging from 0-100 with higher scores indicating better function
Time Frame
2 years post-treatment (up to approximately 27 months post neck dissection)
Title
Median Change in Quality of Life (QOL) From Baseline to 24 Months Post Treatment
Description
Four QOL instruments will be administered: the University of Washington Quality of Life (UWQOL), University of Michigan Head and Neck Quality of Life Instrument (HN-QOL), the University of Michigan Voice Related Quality of Life Measure (V-RQOL), and the FACT Head and Neck (version 4) (FACT H&N). Results of each of the 4 surveys will be reported in separate rows in the results table. The difference in scores from baseline to 24 months after completion of study treatment is calculated for each participant, with the median across all participants reported for each survey. Higher scores indicate better QOLs. Range for Questionnaires: HN QOLs: -100 to +100 VR QOLs: -100 to +100 UW QOLs: -100 to +100 FACTHN Physical: -28 to +28 FACTHN Social: -28 to +28 FACTHN Emotional: -24 to +24 FACTHN Functional: -28 to +28 FACTHN subscale: -40 to +40 FACTHN Total: -148 to +148
Time Frame
2 years post-treatment (up to approximately 27 months post neck dissection)
Title
Disease Specific Survival (DSS)
Description
Proportion of patients alive at 3 years from date of neck dissection. Death from OPSCC (Oropharyngeal Squamous Cell Cancer) will be considered an event for DSS. Death from other causes will be censored at time of death.
Time Frame
3 Years
Title
Progression Free Survival (PFS)
Description
Proportion of patients alive and free of disease persistence, progression or recurrence at 3 years from the date of completion of study treatment. Persistent disease at completion of treatment, post-treatment recurrence or disease specific death will be defined events for progression free survival (PFS).
Time Frame
3 Years
Title
Overall Survival (OS)
Description
Proportion of patients alive at 3 years from date of neck dissection. Death from any cause will be considered an event for overall survival.
Time Frame
3 Years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have pathologically-confirmed, previously untreated, p16-positive oropharyngeal squamous cell carcinoma Patients must have pretreatment neck and chest imaging Tumors must be potentially surgically resectable via a transoral approach, at the discretion of the treating surgeon Patients with T stage T1-3 Patients with N stage N0-N2c ECOG (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death.) Performance status 0-2 Patients are adults (Age >18) Patients must agree to biospecimen submission for tissue and serum processing and storage for secondary biomarker studies Patients must give documented informed consent to participate in this study. Patients must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of chemoradiation (treatment) and for 3 months after discontinuing treatment. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to starting treatment. Women of child-bearing potential, unless they are using highly effective methods of contraception during dosing and for 30 days after study treatment. Women not of childbearing potential will be defined as all women older than age 50 and anovulatory for 12 months. Sexually active males must use a condom during intercourse while receiving chemoradiation and for 90 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Likewise, male subjects should not donate sperm during the time they are receiving chemoradiation and for 90 days after stopping treatment. Exclusion Criteria: Prior head and neck radiation or prior chemotherapy for HNSCC (Head and Neck Squamous Cell Carcinoma) Patients with T4 disease Patients with N3 disease FNA evidence of squamous cell carcinoma involving 3 or more lymph nodes Patients with matted lymph nodes, defined as three nodes abutting one another with loss of intervening fat plane that is a replaced with radiologic evidence of extracapsular spread Patients with an outside primary site biopsy showing perineural or perivascular invasion Documented evidence of distant metastases. Active infection Patients residing in prison. Age < 18 years Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification Unstable angina or a history of myocardial ischemia within prior 6 months Patients with any of the following laboratory values at baseline: Absolute neutrophil count (ANC) < 1,000/mm3 Platelets < 75,000/mm3 Hemoglobin < 9.0 gm/dL Calculated or measured creatinine clearance (method determined by the prescribing physicians) < 50 ml/min Bilirubin > 1.5 x ULN (Upper Limit of Normal), except for patients with known Gilbert syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN Aspartate transaminase (AST) > 3.0 x ULN Alanine transaminase (ALT) > 3.0 x ULN Pregnancy or breastfeeding female. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Swiecicki, M.D.
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

Phase II Treatment Stratification Trial Using Neck Dissection-Driven Selection to Improve Quality of Life for Low Risk Patients With HPV+ Oropharyngeal Squamous Cell Cancer

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