Risk Adapted De-Intensification of Radio-Chemotherapy for Oropharyngeal Squamous Cell Carcinoma

NCT05268614 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: UF-HN-004OCR41015
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 3

Brief Summary

This study builds on the results of several prior studies that we have been involved with to test the hypothesis that Risk-Adapted De-Intensification of Radiation Therapy and chemotherapy based on HPV subtype, plasma circulating free HPV DNA (cfHPV DNA) level, and cfHPV DNA clearance rate produces Local-Regional Control rates that are similar to what has been achieved with more aggressive therapy in patients with Favorable Prognosis Oropharyngeal Squamous Cell Carcinoma (OPSCC).

Conditions

Oropharyngeal Squamous Cell Carcinoma

Keywords

Oropharyngeal Squamous Cell Carcinoma; chemo-radiotherapy; cfHPV DNA

Outcome Measures

Primary Outcomes (1)

• Local-Regional Control Rate

  Determine the Local-Regional Control Rate, defined as the absence of recurrence of OPSCC at the primary site or in a neck node that was included in a radiation therapy target volume

  2 years

Secondary Outcomes (8)

• Local Control Rate

  2 years

• Regional Control Rate

  2 years

• Disease-Free Survival

  2 years

• Distant Metastasis-Free Survival

  2 years

• Overall Survival

  2 years

Study Arms (1)

Chemo-radiotherapy

EXPERIMENTAL

Participants will receive chemo-radiotherapy.

Radiation: Radiation therapy; Drug: Cisplatin

Interventions

Radiation therapy RADIATION

Participants will receive either 70 gray (Gy), 60 Gy, or 50 Gy of radiation based on the following criteria: 70 Gy: Pretreatment level of plasma circulating free HPV DNA (cfHPV DNA) ≤ 3 copies/mL 60 Gy: Tumor tissue positive for HPV subtype other than 16 OR Pretreatment level of cfHPV DNA 4-99 copies/mL OR Pretreatment level of cfHPV DNA ≥ 100 copies/mL AND \<95% decrease in the level cfHPV DNA by the end of week 4 of radiation therapy 50 Gy: Tumor tissue positive for HPV subtype 16, pretreatment level of cfHPV DNA ≥ 100 copies/mL, AND ≥ 95% decrease in the level cfHPV DNA by the end of week 4 of radiation therapy

Chemo-radiotherapy

Cisplatin DRUG

All participants will receive 40 mg/m2 of cisplatin intravenously over 60 minutes weekly during radiation therapy. If cisplatin is not recommended by the treating medical oncologist or is not tolerated, it is permissible to switch to an alternative chemotherapy regimen per institutional practice, but chemotherapy should not be discontinued unless mandated by the patient's condition.

Chemo-radiotherapy

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age (no upper age limit)
• T0-3, N0 to N2, M0 squamous cell carcinoma of the oropharynx by AJCC 8th Edition staging. If T0 the adenopathy must be predominantly in Level 2.
• Tissue diagnosis of HPV and/or p16 positivity from the primary site or an associated lymph node.
• Radiologic confirmation of the absence of lung metastasis within 12 weeks prior to treatment; at a minimum, CT of the chest is required. PET-CT is acceptable.
• ECOG Performance Status 0-2
• ≤10 pack-years of smoking or no smoking for ≥ 10 years
• Eligible for chemotherapy
• CBC/differential obtained within 12 weeks prior to treatment, with adequate bone marrow function defined as follows:
• Platelets ≥ 100,000 cells/mm3
• Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
• Adequate renal and hepatic function within 12 weeks prior to treatment, defined as follows:
• Serum creatinine \< 2.0 mg/dl
• Total bilirubin \< 2 x the institutional ULN (upper limit of normal)
• AST or ALT \< 3 x the institutional ULN
• Note that physician attestation of patient having no known history of liver disease can take the place of bilirubin and AST/ALT labs.

You may not qualify if:

• Prior radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC) OR to the head and neck that, if combined with the protocol therapy, is deemed likely to compromise critical organs at risk in the opinion of the investigator.
• Prior cancer within the last 10 years.
• Prior surgery with curative intent for this OPSCC.
• Patients who have undergone tonsillectomy for diagnosis or excisional biopsy of a neck node for diagnosis are eligible provided there is "gross" cancer present at the primary site or in the neck at the start of radiation therapy on this protocol with "gross" defined as visible on an imaging study.
• Inhalation smoking of tobacco within the last 10 years with \> 10 pack-year equivalent history.
• Currently taking Disease Modifying Rheumatoid Drugs (DMRDs) or immunosuppressive medication, for example as for organ transplant or multiple sclerosis.
• Severe, active co-morbidity, defined as follows:
• Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
• Transmural myocardial infarction within the last 6 months
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; Note, however, coagulation parameters are not required for entry into this protocol.
• Evidence of ACTIVE systemic lupus or scleroderma
• Psoriatic arthritis
• Known HIV positivity. HIV positive patients are known to have worse clinical outcomes especially for local, regional, and distant cancer control. This poorer prognosis is thought to be secondary to a compromised immune system. Thus, de-intensification of radiation and chemotherapy is not justifiable in this population. HIV testing at the time of enrollment is not required.

Sponsors & Collaborators

• University of Florida: lead
• Naveris, Inc.: collaborator

Study Sites (3)

University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

UF Health Proton Therapy Institute

Jacksonville, Florida, 32206, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

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

Study Officials

• Robert Amdur, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Teresa Ware, MPH

CONTACT

352-273-5739; PMO@cancer.ufl.edu

Study Design

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

Study Record Dates

• First Submitted: February 24, 2022
• First Posted: March 7, 2022
• Study Start: May 16, 2022
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2032
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (3)