Trials / Active Not Recruiting

Active Not RecruitingNCT03952585

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

A Randomized Phase II/III Trial of De-Intensified Radiation Therapy for Patients With Early-Stage, P16-Positive, Non-Smoking Associated Oropharyngeal Cancer

Status: Active Not Recruiting
Phase: Phase 2 / Phase 3
Study type: Interventional
Enrollment: 384 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVES: I. To demonstrate non-inferiority in terms of progression-free survival (PFS) of concurrent reduced-dose radiation therapy (RT) with cisplatin or concurrent reduced-dose radiation therapy with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase II) (Arm 2 \[concurrent reduced-dose RT with cisplatin\] was dropped after interim futility analysis in phase II.) II. To demonstrate non-inferiority in terms of progression-free survival (PFS) of concurrent reduced-dose radiation therapy (RT) with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase II) III. To demonstrate co-primary endpoints of non-inferiority of PFS and superiority of quality of life (QOL) as measured by the MD Anderson Dysphagia Inventory (MDADI) of concurrent reduced-dose radiation with cisplatin or concurrent reduced-dose radiation with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase III) (Arm 2 \[concurrent reduced-dose RT with cisplatin\] was dropped after interim futility analysis in phase II.) IV. To demonstrate co-primary endpoints of non-inferiority of PFS and superiority of quality of life (QOL) as measured by the MD Anderson Dysphagia Inventory \[MDADI\] of concurrent reduced-dose radiation with nivolumab to the current standard of care (standard-dose RT with cisplatin). (Phase III) SECONDARY OBJECTIVES: I. To compare patterns of failure (local and regional relapse versus distant) and overall survival between the experimental arm and the control arm. II. To assess long term PFS, overall survival, and toxicity between the experimental arm and the control arm. III. To determine acute and late toxicity profiles as measured by the Common Terminology Criteria for Adverse Events (CTCAE). IV. To explore the symptomatic adverse events (AEs) for tolerability of each treatment arm as measured by the Patient-Reported Outcomes (PRO)-CTCAE. V. To compare changes in patient-reported outcomes (Hearing Handicap Inventory for Adults-Screening \[HHIA-S\], European Organization for Research and Treatment of Cancer \[EORTC\]-Quality of Life Questionnaire \[QLQ\]30) between the experimental arm and the control arm. VI. To assess the association of fludeoxyglucose F-18 (FDG)-positron emission tomography (PET)/computed tomography (CT) at baseline with locoregional control and PFS. VII. To estimate the negative predictive value of the 12-14 weeks post-radiation therapy (RT) FDG-PET/CT in terms of locoregional control rates and PFS rates at 1 and 2 years. EXPLORATORY OBJECTIVES: I. To collect blood and tissue specimens for future translation research. II. To optimize radiotherapy treatment plan quality assurance methodology for radiotherapy planning and imaging. III. To compare changes in patient-reported outcomes (European Quality of Life Five Dimension Five Level Scale \[EQ-5D-5L\]) between the experimental arm and the control arm. IV. To collect Modified Barium Swallow (MBS) data for future review and analysis. OUTLINE: PHASE II: Patients are randomized to 1 of 3 arms. ARM I: Patients undergo standard dose RT as 70 Gy intensity modulated radiation therapy (IMRT) or image-guided radiation therapy (IGRT) over 6 fractions per week and receive 100 mg/m\^2/day cisplatin intravenously (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 fludeoxyglucose F-18 (FDG) and undergo positron emission tomography (PET)/computed tomography (CT) or CT during screening and during follow up, and undergo magnetic resonance imaging (MRI) during follow up. Patients may also undergo tissue biopsy and blood sample collection throughout the study. ARM II (CLOSED TO ACCRUAL 03-FEB-2023): Patients undergo reduced dose RT as 60 Gy IMRT or IGRT once daily (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. ARM III: 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. PHASE III: Patients are randomized to Arm I and/or Arm III. After completion of study treatment, patients are followed up at 12-14 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Conditions

Interventions

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

Timeline

Start date: 2019-10-09
Primary completion: 2024-03-01
Completion: 2026-12-11
First posted: 2019-05-16
Last updated: 2026-04-13
Results posted: 2025-05-02

Locations

494 sites across 2 countries: United States, Canada

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT03952585. Inclusion in this directory is not an endorsement.