This phase II trial studies how well chemotherapy, nivolumab, and intensity-modulated radiation therapy work in treating patients with stage III-IV laryngeal or hypopharyngeal cancer. Drugs used in chemotherapy, such as docetaxel and 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. Intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. Thin beams of radiation of different intensities are aimed at the tumor from many angles. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Giving chemotherapy with nivolumab and intensity-modulated radiation therapy may work better in treating patients with laryngeal and hypopharyngeal cancer than standard of care chemotherapy and radiation therapy.
Additional locations may be listed on ClinicalTrials.gov for NCT03894891.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To improve efficacy with respect to laryngectomy-free survival (LFS) at 2-years from time of study registration as the primary endpoint.
SECONDARY OBJECTIVES:
I. To evaluate clinicopathologic and radiologic response.
II. To estimate overall survival (OS).
III. To estimate laryngo-esophageal dysfunction-free survival (LEDFS).
IV. To evaluate safety and toxicity, and quality of life scores.
V. To characterize distinct tumor immunophenotypes and correlate these findings with outcomes.
OUTLINE:
INDUCTION THERAPY: Patients receive docetaxel intravenously (IV), cisplatin IV, and nivolumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients with partial response (PR) or complete response (CR) proceed with Concurrent Immunoradiotherapy.
CONCURRENT IMMUNORADIOTHERAPY: Within 42 days of Induction Therapy completion, patients undergo 33-35 fractions of intensity-modulated radiation therapy (IMRT) Monday-Friday for up to 7 weeks. Patients also receive nivolumab IV over 30 minutes beginning between days 1 and 7. Treatment repeats every 14 days for up to 3 or 4 doses in the absence of disease progression or unacceptable toxicity.
ADJUVANT THERAPY: Within 3-8 weeks of IMRT completion, patients receive nivolumab IV over 30 minutes. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 4 years.
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorRobert I. Haddad
