The Minimalist Trial-2 (MINT-2)

Phase II Trial of Surgery Followed by Risk-Directed Post-Operative Adjuvant Therapy for HPV-Related Oropharynx Squamous Cell Carcinoma: "The Minimalist Trial-2 (MINT-2)"

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer. Oropharynx SCC (OPSCC) is a common sub-type of HNSCC. Each year, 16,000 new cases of OPSCC are diagnosed in the USA. Most cases of OPSCC (>90%) are caused by the human papillomavirus (HPV) and are often cured with current therapy.

However, patients treated with surgery followed by postoperative adjuvant chemotherapy and radiation therapy (POA(C)RT) still experience substantial morbidity. In this highly curable disease, current clinical research interest is focused on investigation of de-escalated therapy, with the goal to reduce treatment-related adverse events (AEs) while maintaining a low recurrence rate.

In this study, patients with HPV-related OPSCC will undergo resection of the primary tumor site and involved/at-risk regional neck nodes. Based on the pathology report, patients will be assigned to:

• Arm 1 (de-POACRT-42 Gy)
• Arm 2A (de-POART-42 Gy)
• Arm 2B (de-POART-37.8 Gy)
• Arm 2C (de-POACRT-30 Gy).

All patients with high-risk pathology will be assigned to Arm 1 whereas patients with intermediate-risk pathology will be randomized (1:1:1) to Arm 2A, Arm 2B, or Arm 2C. Patients with highest-risk pathology and low-risk pathology will be removed from the trial after surgery and will be advised to pursue standard of care options.

Study Overview

• Status: Recruiting
• Conditions: HPV-Related Oropharynx Squamous Cell Carcinoma
• Intervention / Treatment: Procedure: Surgery; Radiation: Radiation therapy; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Estimated): 142
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Douglas Adkins, M.D.; Phone Number: 314-747-8475; Email: dadkins@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Jason Rich, M.D.
      • Sub-Investigator: Patrik Pipkorn, M.D.
      • Sub-Investigator: Anthony J Apicelli, M.D., Ph.D.
      • Contact: Douglas Adkins, M.D.; Phone Number: 314-747-8475; Email: dadkins@wustl.edu
      • Principal Investigator: Douglas Adkins, M.D.
      • Sub-Investigator: Peter Oppelt, M.D.
      • Sub-Investigator: Esther Lu, Ph.D.
      • Sub-Investigator: Ryan Jackson, M.D.
      • Sub-Investigator: Wade Thorstad, M.D.
      • Sub-Investigator: Brendan Knapp, M.D.
      • Sub-Investigator: Jennifer De Los Santos, M.D.
      • Sub-Investigator: Nikhil Rammohan, M.D., Ph.D.
      • Sub-Investigator: R. Alex Harbison, M.D., M.S.
      • Sub-Investigator: Sid Puram, M.D., Ph.D.
      • Sub-Investigator: Sana Karam, M.D., Ph.D.
      • Sub-Investigator: Christine Auberle, M.D.
      • Sub-Investigator: Jesse Zaretsky, M.D., Ph.D.
      • Sub-Investigator: Ben Wahle, M.D.
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Not yet recruiting
      • Sanford Roger Maris Cancer Center
      • Contact: Daniel Almquist, M.D.; Phone Number: 701-234-6161
      • Principal Investigator: Daniel Almquist, M.D.
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Not yet recruiting
      • Sanford Cancer Center
      • Principal Investigator: Steven Powell, M.D.
      • Contact: Steven Powell, M.D.; Phone Number: 605-328-8000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically or cytologically confirmed HPV-related, clinical stages I-II OPSCC (8th edition of AJCC/UICC Staging Manual) or HPV-related neck node with unknown primary. Clinical T1N0M0 and T2N0M0 disease are excluded. HPV-related may be defined by p16 IHC stain and/or HPV-High Risk RNA ISH/HPV DNA genotyping by PCR, using standard definitions of positive and negative test results.
• Planned resection of the primary tumor site by a transoral approach (TORS, TLM, or conventional surgery).
• Planned unilateral or contralateral selective neck dissection.
• ECOG PS 0-2.

• Adequate organ and marrow function defined as:

  • Creatinine clearance ≥ 50 mL/min.
  • ANC ≥ 1.0 K/cumm.
  • Platelet count ≥100 K/cumm.
• 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.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

• Clinical T1N0M0 or T2N0M0 disease.
• Prior radiation therapy for HNSCC.
• Planned free-flap reconstruction of the resected primary site.
• Cirrhosis with Child-Pugh Score B or C.
• 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 OS > 90%) that were treated with curative-intent therapy.
• 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 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: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Radiation therapy + Cisplatin; Standard of care surgery will occur before adjuvant therapy.; It is recommended that radiation therapy begin within 28 to 49 days (and no later than 56 days).; The total dose to the postoperative tumor bed will be 4200 cGy in 21 fractions of 200 cGy each over 4 weeks.; Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 3780 cGy in 21 fractions of 180 cGy each.; Cisplatin will be given on the same day as one of the initial 5 doses of radiation therapy.	Procedure: Surgery; Standard of care; Radiation: Radiation therapy; IMRT or IMPT; Drug: Cisplatin; Dose of 100 mg/m^2 IVPB over 60 minutes
Experimental: Arm 2A: Radiation therapy; Standard of care surgery will occur before adjuvant therapy.; It is recommended that radiation therapy begin within 28 to 49 days (and no later than 56 days).; The total dose to the postoperative tumor bed will be 4200 cGy in 21 fractions of 200 cGy each over 4 weeks.; Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 3780 cGy in 21 fractions of 180 cGy each.	Procedure: Surgery; Standard of care; Radiation: Radiation therapy; IMRT or IMPT
Experimental: Arm 2B: Radiation therapy; Standard of care surgery will occur before adjuvant therapy.; It is recommended that radiation therapy begin within 28 to 49 days (and no later than 56 days).; The total dose to the postoperative tumor bed will be 3780 cGY in 21 fractions of 180 cGy each over 4 weeks.; Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 3360 cGy in 21 fractions of 160 cGy each.	Procedure: Surgery; Standard of care; Radiation: Radiation therapy; IMRT or IMPT
Experimental: Arm 2C: Radiation therapy + Cisplatin; Standard of care surgery will occur before adjuvant therapy.; It is recommended that radiation therapy begin within 28 to 49 days (and no later than 56 days).; The total dose to the postoperative tumor bed will be 3000 cGy in 15 fractions of 200 cGy over 3 weeks.; Additional regions in the ipsilateral and contralateral neck at risk for microscopic disease in the cervical lymph nodes will receive 2700 cGy in 15 fractions of 180 cGy each.; Cisplatin will be given on the same day as one of the initial 5 doses of radiation therapy.	Procedure: Surgery; Standard of care; Radiation: Radiation therapy; IMRT or IMPT; Drug: Cisplatin; Dose of 100 mg/m^2 IVPB over 60 minutes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrence rate	At 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent weight loss	For assessing percent weight loss, weight (kg) will be collected weekly during radiation within each arm, starting at Day 1 of RT and ending on the last day of RT. The percent weight loss from the baseline is calculated at any post-baseline.	From start of radiation therapy to completion of radiation therapy (estimated to be 6 weeks)
Proportion of patients undergoing PEG tube placement		Through completion of follow-up (estimated to be 5 years and 10 weeks)
Duration of need for an indwelling PEG tube		Through completion of follow-up (estimated to be 5 years and 10 weeks)
Proportion of patients taking narcotic		Through completion of follow-up (estimated to be 5 years and 10 weeks)
Mean change in serum creatinine during radiation therapy	Serum creatinine levels are collected at Day 1 of RT and ending on the last day of RT.	From start of radiation therapy to completion of radiation therapy (estimated to be 6 weeks)
Progression-free survival (PFS)	PFS will be calculated from the date of surgery to the date of progression, death of any cause, or last known date alive.	Through completion of follow-up (estimated to be 5 years and 10 weeks)
Overall survival (OS)	OS will be calculated from the date of surgery to the date of death or last known date alive.	Through completion of follow-up (estimated to be 5 years and 10 weeks)
Number of participants with adverse events		From start of surgery through 24-month follow-up visit (estimated to be 2 years and 10 weeks)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: The Joseph Sanchez Foundation
• 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): April 10, 2025
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): July 15, 2033

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Actual): November 22, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Oropharyngeal cancer; Human papillomavirus; De-escalation; Adjuvant therapy
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Oropharyngeal Neoplasms; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Cisplatin; Radiotherapy; Surgical Procedures, Operative
• Other Study ID Numbers: 202501127

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices), and the study protocol will be shared, beginning 9 months and ending 24 months following article publication, with investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose. Types of acceptable analyses include approved proposal(s) or individual participant data for meta-analyses.
• IPD Sharing Time Frame: Beginning 9 months and ending 24 months following article publication.
• IPD Sharing Access Criteria: Information regarding submitting proposals and accessing data may be submitted to jcley@wustl.edu.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

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.: No