Trials / Terminated

TerminatedNCT04106362

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

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
Phase: Phase 2
Study type: Interventional
Enrollment: 1 (actual)

Sponsor: Jonsson Comprehensive Cancer Center · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Cetuximab	Given IV
DRUG	Cisplatin	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies
RADIATION	Radiation Therapy	Undergo radiation therapy

Timeline

Start date: 2020-01-14
Primary completion: 2023-05-23
Completion: 2023-05-23
First posted: 2019-09-27
Last updated: 2023-06-01

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04106362. Inclusion in this directory is not an endorsement.