The Minimalist Trial-2

Phase 2RecruitingNCT06702033

Washington University School of Medicine142 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

142

Conditions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Recurrence rate

Time frame: At 2 years

Secondary Outcomes

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.

Time frame: From start of radiation therapy to completion of radiation therapy (estimated to be 6 weeks)

Proportion of patients undergoing PEG tube placement

Time frame: Through completion of follow-up (estimated to be 5 years and 10 weeks)

Duration of need for an indwelling PEG tube

Time frame: Through completion of follow-up (estimated to be 5 years and 10 weeks)

Proportion of patients taking narcotic

Time frame: Through completion of follow-up (estimated to be 5 years and 10 weeks)

Number of participants with adverse events

Time frame: From start of surgery through 24-month follow-up visit (estimated to be 2 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.

Time frame: 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.

Time frame: 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.

Time frame: Through completion of follow-up (estimated to be 5 years and 10 weeks)

The Minimalist Trial-2

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts