Surgery Followed by Risk-Directed Post-Operative Adjuvant Therapy for HPV-Related Oropharynx Squamous Cell Carcinoma: The Minimalist Trial (MINT)

Study Overview
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Brief Summary
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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.

Official Title
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Phase II Trial of Surgery Followed by Risk-Directed Post-Operative Adjuvant Therapy for HPV-Related Oropharynx Squamous Cell Carcinoma: The Minimalist Trial (MINT)

Conditions
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HPV Related Oropharyngeal Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Cisplatin
* Radiation: Intensity modulated radiation therapy
* Radiation: Intensity modulated proton therapy
* Procedure: Surgery
* Other: FACT-H&N
* Other: MD Anderson Dysphagia Inventory
* Other: University of Michigan Xerostomia Index
* Other: Scale of Subjective Total Taste Acuity
* Other: Neck Dissection Impairment Index


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: POAmCRT<br>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 | Drug: Cisplatin<br>* -100 mg/m^2 intravenous push bolus (IVPB)<br>* Other names: Platinol-AQ®;Radiation: Intensity modulated radiation therapy<br>* -IMRT or IMPT can be used<br>* Other names: IMRT;Radiation: Intensity modulated proton therapy<br>* -IMRT or IMPT can be used<br>* Other names: IMPT;Procedure: Surgery<br>* -Standard of care<br>Other: FACT-H&N<br>* -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<br>Other: MD Anderson Dysphagia Inventory<br>* -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<br>Other: University of Michigan Xerostomia Index<br>* -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<br>Other: Scale of Subjective Total Taste Acuity<br>* -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<br>Other: Neck Dissection Impairment Index<br>* -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<br>|
| Experimental: Arm 2: POAmRT<br>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 | Radiation: Intensity modulated radiation therapy<br>* -IMRT or IMPT can be used<br>* Other names: IMRT;Radiation: Intensity modulated proton therapy<br>* -IMRT or IMPT can be used<br>* Other names: IMPT;Procedure: Surgery<br>* -Standard of care<br>Other: FACT-H&N<br>* -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<br>Other: MD Anderson Dysphagia Inventory<br>* -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<br>Other: University of Michigan Xerostomia Index<br>* -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<br>Other: Scale of Subjective Total Taste Acuity<br>* -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<br>Other: Neck Dissection Impairment Index<br>* -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<br>|
| Experimental: Arm 3: POACRT<br>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 | Drug: Cisplatin<br>* -100 mg/m^2 intravenous push bolus (IVPB)<br>* Other names: Platinol-AQ®;Radiation: Intensity modulated radiation therapy<br>* -IMRT or IMPT can be used<br>* Other names: IMRT;Radiation: Intensity modulated proton therapy<br>* -IMRT or IMPT can be used<br>* Other names: IMPT;Procedure: Surgery<br>* -Standard of care<br>Other: FACT-H&N<br>* -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<br>Other: MD Anderson Dysphagia Inventory<br>* -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<br>Other: University of Michigan Xerostomia Index<br>* -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<br>Other: Scale of Subjective Total Taste Acuity<br>* -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<br>Other: Neck Dissection Impairment Index<br>* -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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Starting at Day 1 and ending on the last day of radiation therapy (approximately 4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of PEG Tube Placements in Each Arm | -95% confidence intervals will be calculated assuming a binomial distribution | Through completion of follow-up (approximately 63 months) | 
| Change in Serum Creatinine |  | Baseline to 6 weeks after POAmCRT (approximately 90 days) | 
| Percentage of Participants Taking Narcotics | -95% confidence intervals will be calculated assuming a binomial distribution | 6 weeks after POAmCRT (approximately 90 days) | 
| 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) |