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

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

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.

Study Overview

• Status: Completed
• Conditions: HPV Related Oropharyngeal Squamous Cell Carcinoma
• Intervention / Treatment: Procedure: Surgery; Drug: Cisplatin; Radiation: Intensity modulated radiation therapy; Radiation: Intensity modulated proton therapy; 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

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Procedure: Surgery; -Standard of care; Drug: Cisplatin; -100 mg/m^2 intravenous push bolus (IVPB); Other Names: Platinol®; Platinol-AQ®; Radiation: Intensity modulated radiation therapy; -IMRT or IMPT can be used; Other Names: IMRT; Radiation: Intensity modulated proton therapy; -IMRT or IMPT can be used; Other Names: IMPT; Other: FACT-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; Other: MD 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; Other: University 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; Other: Scale 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; Other: Neck 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
Experimental: 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	Procedure: Surgery; -Standard of care; Radiation: Intensity modulated radiation therapy; -IMRT or IMPT can be used; Other Names: IMRT; Radiation: Intensity modulated proton therapy; -IMRT or IMPT can be used; Other Names: IMPT; Other: FACT-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; Other: MD 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; Other: University 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; Other: Scale 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; Other: Neck 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
Experimental: 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	Procedure: Surgery; -Standard of care; Drug: Cisplatin; -100 mg/m^2 intravenous push bolus (IVPB); Other Names: Platinol®; Platinol-AQ®; Radiation: Intensity modulated radiation therapy; -IMRT or IMPT can be used; Other Names: IMRT; Radiation: Intensity modulated proton therapy; -IMRT or IMPT can be used; Other Names: IMPT; Other: FACT-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; Other: MD 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; Other: University 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; Other: Scale 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; Other: Neck 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

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From baseline through one year after completion of treatment (approximately 15 months)
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	From baseline through one year after completion of treatment (approximately 15 months)
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	From baseline through one year after completion of treatment (approximately 15 months)
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	From baseline through one year after completion of treatment (approximately 15 months)
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	From baseline through one year after completion of treatment (approximately 15 months)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Douglas Adkins, M.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2018
• Primary Completion (Actual): March 10, 2021
• Study Completion (Actual): March 17, 2026

Study Registration Dates

• First Submitted: July 26, 2018
• First Submitted That Met QC Criteria: August 2, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Carcinoma, Squamous Cell; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Cisplatin; Surgical Procedures, Operative; Radiotherapy, Intensity-Modulated
• Other Study ID Numbers: 201808045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes