De-intensified Radiation Therapy + Cisplatin/Nivolumab for Oropharyngeal Cancer

Recruiting at 540 trial locations

Overseen by Sue S Yom

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

Research Team

Sue S Yom

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for adults with early-stage, HPV-positive oropharyngeal cancer not linked to smoking. Participants must have a specific type of squamous cell carcinoma, limited smoking history (no more than 10 pack-years), and meet certain health criteria including blood counts and organ function. Those with prior invasive malignancies within 3 years, previous immune therapy, severe allergies to monoclonal antibodies or cisplatin, active autoimmune diseases requiring treatment, or pregnant/nursing women are excluded.

Inclusion Criteria

Clinical stage T1-2, N1, M0 or T3, N0-N1, M0

Pathologically proven diagnosis of squamous cell carcinoma of the oropharynx

Clinically or radiographically evident measurable disease at the primary site or at nodal stations

Exclusion Criteria

Radiographically matted nodes

Supraclavicular nodes

Simultaneous primary cancers or separate bilateral primary tumor sites

Treatment Details

Interventions

• Cisplatin (Chemotherapy)
• Image Guided Radiation Therapy (Radiation)
• Intensity-Modulated Radiation Therapy (Radiation)
• Nivolumab (Checkpoint Inhibitor)

Trial Overview The study compares the effectiveness of reduced radiation therapy combined with nivolumab (an immunotherapy drug) versus standard radiation therapy paired with cisplatin (a chemotherapy drug). The goal is to see if lower doses of radiation can be as effective when used alongside newer treatments like nivolumab in non-smoking related throat cancer caused by HPV.

Participant Groups

Group I: Arm III (IMRT, IGRT, nivolumab) Experimental Treatment 10 Interventions

Beginning 1 week prior to radiation, patients receive 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 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.

Group II: Arm II (IMRT, IGRT, cisplatin) Experimental Treatment 11 Interventions

Patients undergo reduced dose IMRT or IGRT QD over 5 fractions per week and receive 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.

Group III: Arm I (IMRT, IGRT, cisplatin) Active Control 11 Interventions

Patients undergo IMRT or IGRT over 6 fractions per week and receive 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.

Cisplatin is already approved in Canada, Japan for the following indications:

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Stephanie Gaillard

NRG Oncology

Chief Medical Officer

MD from Johns Hopkins University

Norman Wolmark

NRG Oncology

Chief Executive Officer since 2023

MD from Harvard Medical School