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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)

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ClinicalTrials.gov Identifier: NCT03621696
Recruitment Status : Recruiting
First Posted : August 8, 2018
Last Update Posted : July 26, 2019
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

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.

Condition or disease Intervention/treatment Phase
HPV Related Oropharyngeal Squamous Cell Carcinoma 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 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)"
Actual Study Start Date : October 23, 2018
Estimated Primary Completion Date : July 31, 2024
Estimated Study Completion Date : July 31, 2024

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
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 Name: IMRT

Radiation: Intensity modulated proton therapy
-IMRT or IMPT can be used
Other Name: IMPT

Procedure: Surgery
-Standard of care

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
  • 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
-IMRT or IMPT can be used
Other Name: IMRT

Radiation: Intensity modulated proton therapy
-IMRT or IMPT can be used
Other Name: IMPT

Procedure: Surgery
-Standard of care

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
  • 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
-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 Name: IMRT

Radiation: Intensity modulated proton therapy
-IMRT or IMPT can be used
Other Name: IMPT

Procedure: Surgery
-Standard of care

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




Primary Outcome Measures :
  1. Percent weight loss in patients during POAmCRT (Arm 1) [ Time Frame: 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
    • The generalized estimating equation (GEE) model with identity link function will be used to analyze this percent weight loss data, in which the correlation among the repeated measures from the same patient need be considered.


Secondary Outcome Measures :
  1. Proportion of PEG tube placements in each arm [ Time Frame: Through completion of follow-up (approximately 63 months) ]
    -95% confidence intervals will be calculated assuming a binomial distribution

  2. Serum creatinine changes in patients receiving POAmCRT (Arm 1) [ Time Frame: Baseline and 6 weeks after POAmCRT (approximately 90 days) ]
    -The paired t-test will be considered to test the change

  3. Evaluate narcotics administration of patients [ Time Frame: 6 weeks after POAmCRT (approximately 90 days) ]
    -95% confidence intervals will be calculated assuming a binomial distribution

  4. Comparison of quality of life as measured by the FACT-H&N [ Time Frame: From baseline through one year after completion of treatment (approximately 15 months) ]
    • 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

  5. Comparison of quality of life as measured by the MD Anderson Dysphagia Inventory [ Time Frame: From baseline through one year after completion of treatment (approximately 15 months) ]
    • 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

  6. Comparison of quality of life as measured by the University of Michigan Xerostomia Index [ Time Frame: From baseline through one year after completion of treatment (approximately 15 months) ]
    • 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

  7. Comparison of quality of life as measured by the Scale of Subjective Total Taste Acuity [ Time Frame: From baseline through one year after completion of treatment (approximately 15 months) ]
    -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

  8. Comparison of quality of life as measured by the Neck Dissection Impairment Index [ Time Frame: From baseline through one year after completion of treatment (approximately 15 months) ]

    -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


  9. Disease recurrence rate [ Time Frame: 24 months post-treatment (approximately 27 months) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03621696


Contacts
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Contact: Douglas Adkins, M.D. 314-747-8475 dadkins@wustl.edu

Locations
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United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Douglas Adkins, M.D.    314-747-8475    dadkins@wustl.edu   
Principal Investigator: Douglas Adkins, M.D.         
Sub-Investigator: Wade Thorstad, M.D.         
Sub-Investigator: Jose Zevallos, M.D.         
Sub-Investigator: Mackenzie Daly, M.D.         
Sub-Investigator: Ryan Jackson, M.D.         
Sub-Investigator: Jason Rich, M.D.         
Sub-Investigator: Peter Oppelt, M.D.         
Sub-Investigator: Randall Paniello, M.D.         
Sub-Investigator: Patrick Pipkorn, M.D.         
Sub-Investigator: Hiram Gay, M.D.         
Sub-Investigator: Esther Lu, Ph.D.         
Sub-Investigator: Rebecca Chernock, M.D.         
Sub-Investigator: Samir El-Mofty, DMD, M.S., Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Douglas Adkins, M.D. Washington University School of Medicine

Additional Information:
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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT03621696     History of Changes
Other Study ID Numbers: 201808045
First Posted: August 8, 2018    Key Record Dates
Last Update Posted: July 26, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Cisplatin
Antineoplastic Agents