De-intensified Radiation Therapy With Chemotherapy (Cisplatin) or Immunotherapy (Nivolumab) in Treating Patients With Early-Stage, HPV-Positive, Non-Smoking Associated Oropharyngeal Cancer

Conditions

• Basaloid Squamous Cell Carcinoma
• Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Oropharyngeal Squamous Cell Carcinoma
• Papillary Squamous Cell Carcinoma
• Pathologic Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Pathologic Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Squamous Cell Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biopsy Procedure — PROCEDURE
  Undergo tissue biopsy
• Biospecimen Collection — PROCEDURE
  Undergo blood sample collection
• Cisplatin — DRUG
  Given IV
• Computed Tomography — PROCEDURE
  Undergo CT
• Fludeoxyglucose F-18 — OTHER
  Receive FDG
• Image Guided Radiation Therapy — RADIATION
  Undergo IGRT
• Intensity-Modulated Radiation Therapy — RADIATION
  Undergo IMRT
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Nivolumab — BIOLOGICAL
  Given IV
• Positron Emission Tomography — PROCEDURE
  Undergo PET
• Quality-of-Life Assessment — OTHER
  Ancillary studies
• Questionnaire Administration — OTHER
  Ancillary studies

Study Details

This phase II/III trial studies how well a reduced dose of radiation therapy works with nivolumab compared to cisplatin in treating patients with human papillomavirus (HPV)-positive oropharyngeal cancer that is early in its growth and may not have spread to other parts of the body (early-stage), and is not associated with smoking. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial is being done to see if a reduced dose of radiation therapy and nivolumab works as well as standard dose radiation therapy and cisplatin in treating patients with oropharyngeal cancer.

Key Dates

Start date

Oct 9, 2019

Status verified

Dec 2025

Primary completion

Mar 1, 2024

Completion

Dec 11, 2026

Study Design

Enrollment

384 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Arm I (Standard RT + cisplatin)
  Patients undergo standard dose RT as 70 Gy IMRT or IGRT over 6 fractions per week and receive 100 mg/m\^2/day cisplatin IV over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.
• Experimental: Arm II (Reduced RT + cisplatin)
  Patients undergo reduced dose RT as 60 Gy IMRT or IGRT QD over 5 fractions per week and receive 100 mg/m\^2/day cisplatin IV over 30-60 minutes on days 1 and 22. Treatment continues for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.
• Experimental: Arm III (Reduced RT + nivolumab)
  Beginning 1 week prior to radiation, patients receive 240 mg fixed dose nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks (14 days) for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo reduced dose RT as 60 Gy IMRT or IGRT over 6 fractions per week for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients receive FDG and undergo PET/CT or CT during screening and during follow up, and undergo MRI during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study.

Primary Outcome Measure

Progression-free Survival (PFS) (Phase II) (Percentage of Participants Alive Without Progression) [ Time Frame: From randomization to first progression or last follow-up. Maximum follow-up at the time of analysis was 4.6 years. The 1- and 2-year estimates are reported. ]

Locations (493)

Related coverage on Hipa.ai

• Nivolumab in HPV+ Oropharyngeal Cancer: Reduced RT Arms Miss PFS Endpoint
  Nivolumab · May 2, 2025 · ClinicalTrials.gov

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