Radiation Therapy and Cisplatin With or Without Cetuximab in Treating Patients With HPV Positive, KRAS-Variant Stage III-IV Oropharyngeal Squamous Cell Carcinoma

Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Clinical Trial

Official title: Randomized Phase II Trial of Radiotherapy With Concurrent Cisplatin +/- Concurrent Cetuximab for HPV-Positive Oropharyngeal Squamous Cell Carcinoma (OPSCC) in KRAS-Variant Patients

Status Terminated

Clinical Trial Summary

This phase II trial studies how well radiation therapy and cisplatin with or without cetuximab works in treating patients with human papillomavirus (HPV) positive, KRAS-variant stage III-IV oropharyngeal squamous cell carcinoma. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, 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 cetuximab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving radiation therapy, cisplatin, and cetuximab may work better in treating patients with HPV positive, KRAS-variant oropharyngeal squamous cell carcinoma compared to radiation therapy and cisplatin alone.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the efficacy of radiation therapy with concurrent cisplatin combined with concurrent cetuximab in KRAS-variant oropharyngeal squamous cell carcinoma (OPSCC) patients in terms of overall survival (OS) at 2 years.

SECONDARY OBJECTIVES:

I. To determine the efficacy of radiation therapy with concurrent cisplatin combined with concurrent cetuximab in KRAS-variant OPSCC patients in terms of patterns of failure at 6 months and 2 years.

II. To determine the efficacy of radiation therapy with concurrent cisplatin combined with concurrent cetuximab in KRAS-variant OPSCC patients in terms of progression-free survival (PFS) at 2 years.

III. To determine the efficacy of radiation therapy with concurrent cisplatin combined with concurrent cetuximab in KRAS-variant OPSCC patients in terms of locoregional control (LRC) at 2 years.

IV. To determine the efficacy of radiation therapy with concurrent cisplatin combined with concurrent cetuximab in KRAS-variant OPSCC patients in terms of distant metastasis-free survival (DMFS) at 2 and 5 years.

V. To determine the efficacy of radiation therapy with concurrent cisplatin combined with concurrent cetuximab in KRAS-variant OPSCC patients in terms of OS at 5 years.

VI. To determine the safety of radiation therapy with concurrent cisplatin combined with concurrent cetuximab in KRAS-variant OPSCC patients in terms of acute toxicity profiles at the end of radiation, at 1 month, and at 6 months.

VII. To determine the safety of radiation therapy with concurrent cisplatin combined with concurrent cetuximab in KRAS-variant OPSCC patients in terms of late toxicity profiles at 1 and 2 years.

VIII. To determine the safety of radiation therapy with concurrent cisplatin combined with concurrent cetuximab in KRAS-variant OPSCC patients in terms of patient-reported swallowing outcomes at 6 months and 1 and 2 years.

IX. To assess the predictive value of fludeoxyglucose (FDG)-positron emission tomography (PET) at 10-14 weeks post-treatment.

X. To assess the predictive value of additional blood and tissue biomarkers for disease outcomes at 2 years.

EXPLORATORY OBJECTIVES:

I. To evaluate the impact of cetuximab on the immune response as well as treatment outcome and toxicity.

II. To evaluate biomarkers for immune response in HPV-associated OPSCC through saliva and blood samples to be collected prior to treatment and at each follow-up visit.

III. To evaluate for additional checkpoint targets through tumor tissue taken at the time of initial biopsy and profiled for tumor infiltrating lymphocytes, activation markers, and antigen-specific T-cell receptor (TCR) utilization/diversity.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Beginning on day 0, patients undergo radiation therapy over 6 weeks for a total of 35 fractions. Patients also receive cisplatin intravenously (IV) over 1-2 hours on days 0 and 21.

ARM II: Patients receive cetuximab IV over 120 minutes 5-7 days prior to start of radiation therapy and then IV over 60 minutes weekly on Monday or Tuesday for 7 weeks. Patients also undergo radiation therapy and receive cisplatin as in Arm I.

After completion of study treatment, patients are followed up at 2-4 weeks, every 12 weeks for 2 years, and then every 3-12 months for up to 5 years. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• KRAS Protein Variant
• Oropharyngeal Neoplasms
• Pathologic Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Pathologic Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
• Squamous Cell Carcinoma of Head and Neck

• NCT number: NCT04106362
• Study type: Interventional
• Source: Jonsson Comprehensive Cancer Center
• Status: Terminated
• Phase: Phase 2
• Start date: January 14, 2020
• Completion date: May 23, 2023