HPV Related Oropharyngeal Squamous Cell Carcinoma
Conditions
Brief summary
The overarching goal of the MINT trial is to reduce treatment-related toxicity while maintaining efficacy. Patients with HPV-related oropharyngeal squamous cell carcinoma (OPSCC) will undergo resection of the primary tumor site and involved/at risk regional neck nodes.
Interventions
DRUGCisplatin
-100 mg/m\^2 intravenous push bolus (IVPB)
RADIATIONIntensity modulated radiation therapy
-IMRT or IMPT can be used
RADIATIONIntensity modulated proton therapy
-IMRT or IMPT can be used
PROCEDURESurgery
-Standard of care
OTHERFACT-H&N
-Baseline, interim assessment (14-42 days post-surgery), day 1 of radiation, day 21 of radiation, day 36 of radiation, 6 weeks after completion of adjuvant therapy, 4 months after the completion of adjuvant therapy, 6 months after the completion of adjuvant therapy, 12 months after the completion of adjuvant therapy, and 24 months after completion of adjuvant therapy
OTHERMD Anderson Dysphagia Inventory
-Baseline, interim assessment (14-42 days post-surgery), day 1 of radiation, day 21 of radiation, day 36 of radiation, 6 weeks after completion of adjuvant therapy, 4 months after the completion of adjuvant therapy, 6 months after the completion of adjuvant therapy, 12 months after the completion of adjuvant therapy, and 24 months after completion of adjuvant therapy
OTHERUniversity of Michigan Xerostomia Index
-Baseline, interim assessment (14-42 days post-surgery), day 1 of radiation, day 21 of radiation, day 36 of radiation, 6 weeks after completion of adjuvant therapy, 4 months after the completion of adjuvant therapy, 6 months after the completion of adjuvant therapy, 12 months after the completion of adjuvant therapy, and 24 months after completion of adjuvant therapy
OTHERScale of Subjective Total Taste Acuity
-Baseline, interim assessment (14-42 days post-surgery), day 1 of radiation, day 21 of radiation, day 36 of radiation, 6 weeks after completion of adjuvant therapy, 4 months after the completion of adjuvant therapy, 6 months after the completion of adjuvant therapy, 12 months after the completion of adjuvant therapy, and 24 months after completion of adjuvant therapy
OTHERNeck Dissection Impairment Index
-Baseline, interim assessment (14-42 days post-surgery), day 1 of radiation, day 21 of radiation, day 36 of radiation, 6 weeks after completion of adjuvant therapy, 4 months after the completion of adjuvant therapy, 6 months after the completion of adjuvant therapy, 12 months after the completion of adjuvant therapy, and 24 months after completion of adjuvant therapy
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed HPV-related stages I-III OPSCC (8th edition of AJCC/UICC Staging Manual) or HPV-related neck node with unknown primary. HPV-related may be defined by p16 IHC stain and/or HPV-ISH or PCR using standard definitions of positive and negative test results. * Primary tumor that will be resected via a transoral oral approach (conventional surgery, transoral laser microsurgery, transoral robotic surgery) * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2. * Normal organ and marrow function defined as: * Creatinine clearance \> 50 cc/min. * ANC \> 1,000/mcL. * Platelet count \>100,000/mcL. * At least 18 years of age. * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Patient (or legally authorized representative) must be able to understand and willing to sign a written informed consent document.
Exclusion criteria
* Prior curative therapy for HNSCC. * Patient must not have known distant metastatic disease at presentation. * History of prior invasive malignancy diagnosed within 2 years prior to study enrollment; exceptions are malignancies with a low risk of metastasis or death (e.g., expected 5-year overall survival (OS) \> 90%) that were treated with an expected curative outcome, such as squamous cell carcinoma of the skin, in-situ carcinoma of the cervix uteri, non-melanomatous skin cancer, carcinoma in situ of the breast, or incidental histological finding of prostate cancer (TNM stage of T1a or T1b). * Receiving any other investigational agents. * Uncontrolled serious inter-current illness or serious psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and/or breastfeeding. A negative serum or urine pregnancy test is required at screening for all female patients of childbearing potential.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Weight Change | Starting at Day 1 and ending on the last day of radiation therapy (approximately 4 weeks) | * Weight in kilograms will be collected weekly during radiation * The percent weight loss from the baseline is calculated at any post-baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of PEG Tube Placements in Each Arm | Through completion of follow-up (approximately 63 months) | -95% confidence intervals will be calculated assuming a binomial distribution |
| Change in Serum Creatinine | Baseline to 6 weeks after POAmCRT (approximately 90 days) | — |
| Percentage of Participants Taking Narcotics | 6 weeks after POAmCRT (approximately 90 days) | -95% confidence intervals will be calculated assuming a binomial distribution |
| Disease Recurrence Rate | 24 months post-treatment (approximately 27 months) | — |
| Progression-free Survival (PFS) | Through completion of follow-up (approximately 63 months) | — |
| Overall Survival (OS) | Through completion of follow-up (approximately 63 months) | — |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORDouglas Adkins, M.D.
Washington University School of Medicine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: POAmCRT * Patients with extracapsular extension (ECE) or positive margin but not clinical or pathologic T4 or clinical N3 disease
* Standard of care surgery (surgical resection of the primary tumor via a transoral approach and surgical management of cervical lymph nodes
* Treated with post-operative adjuvant modified chemoradiation therapy (POAmCRT) which is 42 Gy radiation therapy in 21 doses and 1 dose of cisplatin.
* It is recommended that radiation therapy begin within 28-49 days (no later than 56 days) after surgical resection
* Intensity modulated radiation therapy (IMRT) or intensity modulated proton therapy (IMPT) is to be used for this study | 21 |
| Arm 2: POAmRT * Patients with no extracapsular extension (ECE) and no positive margins and not clinical or pathologic T4 or clinical N3 disease
* Standard of care surgery (surgical resection of the primary tumor via a transoral approach and surgical management of cervical lymph nodes
* Treated with post-operative adjuvant modified radiation therapy (POAmRT) which is 42 Gy radiation therapy in 21 doses
* It is recommended that radiation therapy begin within 28-49 days (no later than 56 days) after surgical resection
* Intensity modulated radiation therapy (IMRT) or intensity modulated proton therapy (IMPT) is to be used for this study | 31 |
| Arm 3: POACRT * Patients with clinical or pathologic T4 or clinical N3 disease
* Standard of care surgery (surgical resection of the primary tumor via a transoral approach and surgical management of cervical lymph nodes
* Treated with post-operative adjuvant chemoradiation therapy (POACRT) which is 60 Gy radiation therapy in 30 doses and 3 doses of cisplatin (if there is pathologic evidence of ECE or positive margins)
* The first dose of cisplatin will given on one of the days during the initial 5 days of radiation therapy, the 2nd dose on the day of radiation dose 16, and the 3rd dose on the day of radiation dose 26.
* It is recommended that radiation therapy begin within 28-49 days (no later than 56 days) after surgical resection
* Intensity modulated radiation therapy (IMRT) or intensity modulated proton therapy (IMPT) is to be used for this study | 6 |
| Not Assigned to an Arm -Patients were enrolled to the study but deemed ineligible to start treatment and were not enrolled to any arm. | 5 |
| Total | 63 |
Baseline characteristics
| Characteristic | Arm 1: POAmCRT | Total | Not Assigned to an Arm | Arm 3: POACRT | Arm 2: POAmRT |
|---|---|---|---|---|---|
| Age, Continuous | 56 years | 58 years | 57 years | 60 years | 58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 61 Participants | 5 Participants | 6 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 60 Participants | 5 Participants | 5 Participants | 31 Participants |
| Region of Enrollment United States | 21 participants | 63 participants | 5 participants | 6 participants | 31 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 0 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 20 Participants | 58 Participants | 5 Participants | 6 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 31 | 0 / 6 |
| other Total, other adverse events | 21 / 21 | 31 / 31 | 6 / 6 |
| serious Total, serious adverse events | 3 / 21 | 2 / 31 | 2 / 6 |
Outcome results
Primary
Mean Percent Weight Change
* Weight in kilograms will be collected weekly during radiation * The percent weight loss from the baseline is calculated at any post-baseline
Time frame: Starting at Day 1 and ending on the last day of radiation therapy (approximately 4 weeks)
Population: 1 participant not evaluable in Arm 2 and 2 participants not evaluable in Arm 3 as they didn't receive CRT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1: POAmCRT | Mean Percent Weight Change | -4.89 percent of change |
| Arm 2: POAmRT | Mean Percent Weight Change | -3.18 percent of change |
| Arm 3: POACRT | Mean Percent Weight Change | -10.11 percent of change |
Secondary
Change in Serum Creatinine
Time frame: Baseline to 6 weeks after POAmCRT (approximately 90 days)
Population: 1 participant not evaluable in Arm 2 and 2 participants not evaluable in Arm 3 as they didn't receive CRT.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: POAmCRT | Change in Serum Creatinine | 0.03 mg/dL | Standard Deviation 0.09 |
| Arm 2: POAmRT | Change in Serum Creatinine | 0.08 mg/dL | Standard Deviation 0.22 |
| Arm 3: POACRT | Change in Serum Creatinine | -0.19 mg/dL | Standard Deviation 0.19 |
Secondary
Disease Recurrence Rate
Time frame: 24 months post-treatment (approximately 27 months)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1: POAmCRT | Disease Recurrence Rate | 2 Participants |
| Arm 2: POAmRT | Disease Recurrence Rate | 1 Participants |
| Arm 3: POACRT | Disease Recurrence Rate | 3 Participants |
Secondary
Overall Survival (OS)
Time frame: Through completion of follow-up (approximately 63 months)
Secondary
Percentage of Participants Taking Narcotics
-95% confidence intervals will be calculated assuming a binomial distribution
Time frame: 6 weeks after POAmCRT (approximately 90 days)
Population: 1 participant not evaluable in Arm 2 and 2 participants not evaluable in Arm 3 as they didn't receive CRT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: POAmCRT | Percentage of Participants Taking Narcotics | 40 percentage of participants |
| Arm 2: POAmRT | Percentage of Participants Taking Narcotics | 20 percentage of participants |
| Arm 3: POACRT | Percentage of Participants Taking Narcotics | 75 percentage of participants |
Secondary
Progression-free Survival (PFS)
Time frame: Through completion of follow-up (approximately 63 months)
Secondary
Proportion of PEG Tube Placements in Each Arm
-95% confidence intervals will be calculated assuming a binomial distribution
Time frame: Through completion of follow-up (approximately 63 months)
Other Pre-specified
Comparison of Quality of Life as Measured by the FACT-H&N
* Consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, which is further supplemented by 12 site specific items to assess for head and neck related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as an global QoL score. Higher scores represent better QoL. * Captured at baseline, interim assessment (14-42 days post-surgery), Day 1 of radiation, Day 21 after start of radiation, Day 36 after start of radiation, and 6 weeks/4 months/6 months/12 months after completion of adjuvant therapy
Time frame: From baseline through one year after completion of treatment (approximately 15 months)
Other Pre-specified
Comparison of Quality of Life as Measured by the MD Anderson Dysphagia Inventory
* Consists of 20 items. Besides a global assessment (a single question), it comprises three subscales: the emotional subscale (8 items), the functional subscale (5 items), and the physical subscale (6 items). The global assessment refers to the individual's swallowing difficulty as it affects one's overall daily routine. The emotional, functional, and physical subscales refer to the individual's affective response to the swallowing disorder, the impact of the disorder on daily activities, and the self-perception of the swallowing difficulties, respectively. Using a five-point scale (1-5), the minimum total score is 20 and the maximum 100 * Captured at baseline, interim assessment (14-42 days post-surgery), Day 1 of radiation, Day 21 after start of radiation, Day 36 after start of radiation, and 6 weeks/4 months/6 months/12 months after completion of adjuvant therapy
Time frame: From baseline through one year after completion of treatment (approximately 15 months)
Other Pre-specified
Comparison of Quality of Life as Measured by the Neck Dissection Impairment Index
-10-item self-administered questionnaire, which was designed to assess quality of life related to shoulder dysfunction after neck dissection. A 5-point response option (1 to 5) is provided for each item, with 1 being the most disability and 5 the least disability. The responses for all 10 items are added together to produce a raw score, which is then transformed to a score of 100 maximum. Higher scores represent less disability. --Captured at baseline, interim assessment (14-42 days post-surgery), Day 1 of radiation, Day 21 after start of radiation, Day 36 after start of radiation, and 6 weeks/4 months/6 months/12 months after completion of adjuvant therapy
Time frame: From baseline through one year after completion of treatment (approximately 15 months)
Other Pre-specified
Comparison of Quality of Life as Measured by the Scale of Subjective Total Taste Acuity
-Measures total taste acuity with the patient choosing the appropriate answer ranging from 0=same taste acuity as before treatment to 4=almost complete or complete loss of taste acuity
Time frame: From baseline through one year after completion of treatment (approximately 15 months)
Other Pre-specified
Comparison of Quality of Life as Measured by the University of Michigan Xerostomia Index
* Measures impact of salivary gland dysfunction & xerostomia. Scale consists of 15 items covering 4 major domains of oral health-related quality of life: physical functioning, personal/psychological functioning, social functioning, & pain/discomfort issues * Patients answer the questions by checking the box that describes the best statement for the past 7 days (not at all, a little, somewhat, quite a bit, very much), 1-5 scale. Higher scores represent greater degree of symptoms. Physical functioning based upon responses to items 1, 6, 10, 12. Pain/discomfort issues based upon responses to items 2, 3, 7, 9. Personal/psychological functioning based upon responses to items 8, 13, 14, 15. Social functioning based upon responses to items 4, 5, 11 * Captured at baseline, interim assessment (14-42 days post-surgery), Day 1 of radiation, Day 21 after start of radiation, Day 36 after start of radiation, & 6 weeks/4 months/6 months/12 months after completion of adjuvant therapy
Time frame: From baseline through one year after completion of treatment (approximately 15 months)