NCT03621696CompletedPhase 2
Phase II Trial of Surgery Followed by Risk-Directed Post-Operative Adjuvant Therapy for HPV-Related Oropharynx Squamous Cell Carcinoma: "The Minimalist Trial (MINT)"
Washington University School of Medicine2 sites in 1 country63 target enrollmentStarted: October 23, 2018Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 63
- Locations
- 2
- Primary Endpoint
- Mean Percent Weight Change
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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-
- •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.
Arms & Interventions
Arm 1: POAmCRT
Experimental
- 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
Intervention: Surgery (Procedure)
Arm 1: POAmCRT
Experimental
- 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
Intervention: Neck Dissection Impairment Index (Other)
Arm 2: POAmRT
Experimental
- 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
Intervention: Intensity modulated radiation therapy (Radiation)
Arm 3: POACRT
Experimental
- 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: Cisplatin (Drug)
Arm 1: POAmCRT
Experimental
- 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
Intervention: Intensity modulated radiation therapy (Radiation)
Arm 1: POAmCRT
Experimental
- 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
Intervention: Intensity modulated proton therapy (Radiation)
Arm 1: POAmCRT
Experimental
- 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
Intervention: FACT-H&N (Other)
Arm 1: POAmCRT
Experimental
- 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
Intervention: MD Anderson Dysphagia Inventory (Other)
Arm 1: POAmCRT
Experimental
- 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
Intervention: University of Michigan Xerostomia Index (Other)
Arm 1: POAmCRT
Experimental
- 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
Intervention: Scale of Subjective Total Taste Acuity (Other)
Arm 2: POAmRT
Experimental
- 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
Intervention: Intensity modulated proton therapy (Radiation)
Arm 2: POAmRT
Experimental
- 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
Intervention: Surgery (Procedure)
Arm 2: POAmRT
Experimental
- 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
Intervention: FACT-H&N (Other)
Arm 2: POAmRT
Experimental
- 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
Intervention: MD Anderson Dysphagia Inventory (Other)
Arm 2: POAmRT
Experimental
- 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
Intervention: University of Michigan Xerostomia Index (Other)
Arm 2: POAmRT
Experimental
- 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
Intervention: Scale of Subjective Total Taste Acuity (Other)
Arm 2: POAmRT
Experimental
- 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
Intervention: Neck Dissection Impairment Index (Other)
Arm 3: POACRT
Experimental
- 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: Intensity modulated radiation therapy (Radiation)
Arm 3: POACRT
Experimental
- 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: Intensity modulated proton therapy (Radiation)
Arm 3: POACRT
Experimental
- 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: Surgery (Procedure)
Arm 3: POACRT
Experimental
- 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: FACT-H&N (Other)
Arm 3: POACRT
Experimental
- 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: MD Anderson Dysphagia Inventory (Other)
Arm 3: POACRT
Experimental
- 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: University of Michigan Xerostomia Index (Other)
Arm 3: POACRT
Experimental
- 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: Scale of Subjective Total Taste Acuity (Other)
Arm 3: POACRT
Experimental
- 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: Neck Dissection Impairment Index (Other)
Arm 1: POAmCRT
Experimental
- 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
Intervention: Cisplatin (Drug)
Outcomes
Primary Outcomes
Mean Percent Weight Change
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
Secondary Outcomes
- Change in Serum Creatinine(Baseline to 6 weeks after POAmCRT (approximately 90 days))
- Percentage of Participants Taking Narcotics(6 weeks after POAmCRT (approximately 90 days))
- Overall Survival (OS)(Through completion of follow-up (approximately 63 months))
- Proportion of PEG Tube Placements in Each Arm(Through completion of follow-up (approximately 63 months))
- Progression-free Survival (PFS)(Through completion of follow-up (approximately 63 months))
- Disease Recurrence Rate(24 months post-treatment (approximately 27 months))
Investigators
Study Sites (2)
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