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

Primary Purpose

HPV Related Oropharyngeal Squamous Cell Carcinoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cisplatin
Intensity modulated radiation therapy
Intensity modulated proton therapy
Surgery
FACT-H&N
MD Anderson Dysphagia Inventory
University of Michigan Xerostomia Index
Scale of Subjective Total Taste Acuity
Neck Dissection Impairment Index
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HPV Related Oropharyngeal Squamous Cell Carcinoma

Eligibility Criteria

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

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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Arm 1: POAmCRT

Arm 2: POAmRT

Arm 3: POACRT

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Proportion of PEG Tube Placements in Each Arm
-95% confidence intervals will be calculated assuming a binomial distribution
Change in Serum Creatinine
Percentage of Participants Taking Narcotics
-95% confidence intervals will be calculated assuming a binomial distribution
Disease Recurrence Rate
Progression-free Survival (PFS)
Overall Survival (OS)

Full Information

First Posted
July 26, 2018
Last Updated
October 4, 2023
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT03621696
Brief Title
Surgery Followed by Risk-Directed Post-Operative Adjuvant Therapy for HPV-Related Oropharynx Squamous Cell Carcinoma: "The Minimalist Trial (MINT)"
Acronym
MINT
Official Title
Phase II Trial of Surgery Followed by Risk-Directed Post-Operative Adjuvant Therapy for HPV-Related Oropharynx Squamous Cell Carcinoma: "The Minimalist Trial (MINT)"
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 23, 2018 (Actual)
Primary Completion Date
March 10, 2021 (Actual)
Study Completion Date
March 10, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HPV Related Oropharyngeal Squamous Cell Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: POAmCRT
Arm Type
Experimental
Arm Description
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
Arm Title
Arm 2: POAmRT
Arm Type
Experimental
Arm Description
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
Arm Title
Arm 3: POACRT
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Platinol®, Platinol-AQ®
Intervention Description
-100 mg/m^2 intravenous push bolus (IVPB)
Intervention Type
Radiation
Intervention Name(s)
Intensity modulated radiation therapy
Other Intervention Name(s)
IMRT
Intervention Description
-IMRT or IMPT can be used
Intervention Type
Radiation
Intervention Name(s)
Intensity modulated proton therapy
Other Intervention Name(s)
IMPT
Intervention Description
-IMRT or IMPT can be used
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
-Standard of care
Intervention Type
Other
Intervention Name(s)
FACT-H&N
Intervention Description
-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
Intervention Type
Other
Intervention Name(s)
MD Anderson Dysphagia Inventory
Intervention Description
-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
Intervention Type
Other
Intervention Name(s)
University of Michigan Xerostomia Index
Intervention Description
-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
Intervention Type
Other
Intervention Name(s)
Scale of Subjective Total Taste Acuity
Intervention Description
-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
Intervention Type
Other
Intervention Name(s)
Neck Dissection Impairment Index
Intervention Description
-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
Primary Outcome Measure Information:
Title
Mean Percent Weight Change
Description
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)
Secondary Outcome Measure Information:
Title
Proportion of PEG Tube Placements in Each Arm
Description
-95% confidence intervals will be calculated assuming a binomial distribution
Time Frame
Through completion of follow-up (approximately 63 months)
Title
Change in Serum Creatinine
Time Frame
Baseline to 6 weeks after POAmCRT (approximately 90 days)
Title
Percentage of Participants Taking Narcotics
Description
-95% confidence intervals will be calculated assuming a binomial distribution
Time Frame
6 weeks after POAmCRT (approximately 90 days)
Title
Disease Recurrence Rate
Time Frame
24 months post-treatment (approximately 27 months)
Title
Progression-free Survival (PFS)
Time Frame
Through completion of follow-up (approximately 63 months)
Title
Overall Survival (OS)
Time Frame
Through completion of follow-up (approximately 63 months)
Other Pre-specified Outcome Measures:
Title
Comparison of Quality of Life as Measured by the Neck Dissection Impairment Index
Description
-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)
Title
Comparison of Quality of Life as Measured by the Scale of Subjective Total Taste Acuity
Description
-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)
Title
Comparison of Quality of Life as Measured by the University of Michigan Xerostomia Index
Description
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)
Title
Comparison of Quality of Life as Measured by the MD Anderson Dysphagia Inventory
Description
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)
Title
Comparison of Quality of Life as Measured by the FACT-H&N
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Douglas Adkins, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

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