The Minimalist Trial-2

NCT06702033 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 202501127
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 3

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.

Conditions

HPV-Related Oropharynx Squamous Cell Carcinoma

Keywords

De-escalation; Adjuvant therapy; Oropharyngeal cancer; Human papillomavirus

Outcome Measures

Primary Outcomes (1)

• Recurrence rate

  At 2 years

Secondary Outcomes (8)

• Percent weight loss

  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)

• Number of participants with adverse events

  From start of surgery through 24-month follow-up visit (estimated to be 2 years and 10 weeks)

Study Arms (4)

Arm 1: Radiation therapy + Cisplatin

EXPERIMENTAL

* 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; Drug: Cisplatin; Procedure: Surgery

Arm 2A: Radiation therapy

EXPERIMENTAL

* 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; Procedure: Surgery

Arm 2B: Radiation therapy

EXPERIMENTAL

* 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; Procedure: Surgery

Arm 2C: Radiation therapy + Cisplatin

EXPERIMENTAL

* 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; Drug: Cisplatin; Procedure: Surgery

Interventions

Radiation therapy RADIATION

IMRT or IMPT

Arm 1: Radiation therapy + Cisplatin; Arm 2A: Radiation therapy; Arm 2B: Radiation therapy; Arm 2C: Radiation therapy + Cisplatin

Cisplatin DRUG

Dose of 100 mg/m\^2 IVPB over 60 minutes

Arm 1: Radiation therapy + Cisplatin; Arm 2C: Radiation therapy + Cisplatin

Surgery PROCEDURE

Standard of care

Arm 1: Radiation therapy + Cisplatin; Arm 2A: Radiation therapy; Arm 2B: Radiation therapy; Arm 2C: Radiation therapy + Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• The Joseph Sanchez Foundation: collaborator

Study Sites (3)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58102, United States

NOT YET RECRUITING

Sanford Cancer Center

Sioux Falls, South Dakota, 57104, United States

NOT YET RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Oropharyngeal Neoplasms

Interventions

Radiotherapy; Cisplatin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Douglas Adkins, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Douglas Adkins, M.D.

CONTACT

314-747-8475; dadkins@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: * 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.

Study Record Dates

• First Submitted: November 19, 2024
• First Posted: November 22, 2024
• Study Start: April 10, 2025
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): July 15, 2033
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 24 months following article publication.
• Access Criteria: Information regarding submitting proposals and accessing data may be submitted to jcley@wustl.edu.

Locations

US (3)