Washington University in St. Louis

The Minimalist Trial-2

Purpose

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.

Condition

HPV-Related Oropharynx Squamous Cell Carcinoma

Eligibility

Eligible Ages: Over 18 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

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 Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
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
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
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.	Radiation: Radiation therapy IMRT or IMPT Drug: Cisplatin Dose of 100 mg/m^2 IVPB over 60 minutes Procedure: Surgery Standard of care
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.	Radiation: Radiation therapy IMRT or IMPT Procedure: Surgery Standard of care
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.	Radiation: Radiation therapy IMRT or IMPT Procedure: Surgery Standard of care
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.	Radiation: Radiation therapy IMRT or IMPT Drug: Cisplatin Dose of 100 mg/m^2 IVPB over 60 minutes Procedure: Surgery Standard of care

Recruiting Locations

Washington University in St. Louis and nearby locations

Washington University School of Medicine
St Louis 4407066, Missouri 4398678 63110

Contact:
Douglas Adkins, M.D.
314-747-8475
dadkins@wustl.edu

More Details

NCT ID: NCT06702033
Status: Recruiting
Sponsor: Washington University School of Medicine

Study Contact

Douglas Adkins, M.D.
314-747-8475
dadkins@wustl.edu

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.