Clinical Trials /

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

NCT03621696

Description:

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.

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 201808045
  • NCT ID: NCT03621696

Conditions

  • HPV Related Oropharyngeal Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
CisplatinPlatinol®, Platinol-AQ®Arm 1: POAmCRT

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Arm 1: POAmCRTExperimentalPatients 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
  • Cisplatin
Arm 2: POAmRTExperimentalPatients 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
    Arm 3: POACRTExperimentalPatients 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
    • Cisplatin

    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.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure: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)
    Safety Issue:
    Description: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

    Measure:Proportion of PEG tube placements in each arm
    Time Frame:Through completion of follow-up (approximately 63 months)
    Safety Issue:
    Description:-95% confidence intervals will be calculated assuming a binomial distribution
    Measure:Serum creatinine changes in patients receiving POAmCRT (Arm 1)
    Time Frame:Baseline and 6 weeks after POAmCRT (approximately 90 days)
    Safety Issue:
    Description:-The paired t-test will be considered to test the change
    Measure:Evaluate narcotics administration of patients
    Time Frame:6 weeks after POAmCRT (approximately 90 days)
    Safety Issue:
    Description:-95% confidence intervals will be calculated assuming a binomial distribution
    Measure: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)
    Safety Issue:
    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
    Measure: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)
    Safety Issue:
    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
    Measure: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)
    Safety Issue:
    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
    Measure: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)
    Safety Issue:
    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
    Measure: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)
    Safety Issue:
    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
    Measure:Disease recurrence rate
    Time Frame:24 months post-treatment (approximately 27 months)
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Washington University School of Medicine

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