Clinical trial NCT06702033: The Minimalist Trial-2
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-2 (MINT-2)"
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: HPV-Related Oropharynx Squamous Cell Carcinoma
Keywords: De-escalation
Adjuvant therapy
Oropharyngeal cancer
Human papillomavirus
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: The Joseph Sanchez Foundation
First posted: 2024-11-22
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: * Highest risk pathology (pT4) = remove from trial.
* High-risk pathology = Arm 1
* Intermediate-risk pathology will be randomized to Arm 2A, Arm 2B, or Arm 2C.
* Low-risk pathology = remove from trial.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Recurrence rate
timeFrame: At 2 years
Secondary outcomes:
measure: Percent weight loss
timeFrame: From start of radiation therapy to completion of radiation therapy (estimated to be 6 weeks)
measure: Proportion of patients undergoing PEG tube placement
timeFrame: Through completion of follow-up (estimated to be 5 years and 10 weeks)
measure: Duration of need for an indwelling PEG tube
timeFrame: Through completion of follow-up (estimated to be 5 years and 10 weeks)
measure: Proportion of patients taking narcotic
timeFrame: Through completion of follow-up (estimated to be 5 years and 10 weeks)
measure: Number of participants with adverse events
timeFrame: From start of surgery through 24-month follow-up visit (estimated to be 2 years and 10 weeks)
measure: Mean change in serum creatinine during radiation therapy
timeFrame: From start of radiation therapy to completion of radiation therapy (estimated to be 6 weeks)
measure: Progression-free survival (PFS)
timeFrame: Through completion of follow-up (estimated to be 5 years and 10 weeks)
measure: Overall survival (OS)
timeFrame: Through completion of follow-up (estimated to be 5 years and 10 weeks)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Douglas Adkins, M.D.
role: PRINCIPAL_INVESTIGATOR
References: