Intensity-Modulated Radiation Therapy & Nivolumab for Recurrent or Second Primary Head & Neck Squamous Cell Cancer

Phase II Study of IMRT Re-Irradiation With Concurrent/Adjuvant Nivolumab in Patients With Locoregionally Recurrent or Second Primary Squamous Cell Cancer of the Head and Neck

This phase II trial studies how well intensity-modulated radiotherapy and nivolumab work together in treating patients with head and neck squamous cell cancer that has come back. Intensity-modulation radiation therapy uses varying intensities of radiation beams to kill cancer cells and shrink tumors, thereby reducing the damage to nearby healthy tissue. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving intensity-modulated radiation therapy and nivolumab may work better at treating head and neck squamous cell cancer.

Study Overview

• Status: Completed
• Conditions: Recurrent Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Biological: Nivolumab; Radiation: IMRT

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the 1-year progression-free survival (PFS) for patients with recurrent or second primary head and neck squamous cancer treated with intensity-modulated radiation therapy (IMRT) re-irradiation with concurrent and adjuvant nivolumab.

SECONDARY OBJECTIVES:

I. Evaluate the 1-year (yr) overall survival (OS) of patients treated with re-irradiation and nivolumab.

II. Evaluate patient quality of life (QOL).

III. Evaluate patterns of failure including local, regional and distant failure rates at 1 yr.

IV. Identify and estimate the incidence rate of acute and late toxicities associated with combined re-irradiation and concurrent and adjuvant nivolumab.

TERTIARY OBJECTIVE:

I. To identify potential biomarkers related to clinical benefit to concurrent and adjuvant nivolumab and re-irradiation in patients with recurrent or second primary (RSP) head and neck squamous cell carcinoma (HNSCC).

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on weeks -2, 0, 2, 4, and 6 and undergo IMRT once daily beginning on week 0 for up to 6-6.5 weeks. Beginning week 10, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years from the beginning of radiation therapy.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field
• Life expectancy of greater than 6 months
• Patients cannot have distant metastases and have to be candidates for curative re-irradiation
• Patients with salivary gland tumors are excluded (patients with nasopharynx or sinonasal cancers can participate)
• Patients with unresectable disease are eligible

• Patients who undergo surgical resection will be allowed regardless of human papilloma virus (HPV) status provided they have one of the following criteria:

  • Positive margins on pathology
  • Evidence of extracapsular spread on nodal pathology
  • Gross residual disease on postoperative or simulation imaging
  • N2/3 disease
  • T3/4 disease
  • Multifocal perineural invasion and/or lymphovascular space invasion
• The majority of the anticipated target volume (> 50%) must have been previously treated to ≥ 40 Gy; prior radiation therapy (RT) must have been completed > 6 months prior to initiation of IMRT reirradiation; if previous RT records are unavailable, investigators can estimate the dose to previously treated tissues based on completion notes or other treatment history
• An Eastern Cooperative Oncology Group (ECOG) performance score 0-2
• Granulocytes > 1500/mm³
• Platelets > 100,000/mm³
• Bilirubin < 1.5 mg/dl
• Creatinine < 1.5 mg/dl
• No other concurrent invasive malignancies treated for the past year (localized prostate cancer or early stage skin cancer are not exclusion criteria)
• Patients with carotid artery involvement or encasement will be allowed provided they have no symptoms related to carotid involvement
• No prior exposure to immunotherapy agents
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Any known factors that would pose a contraindication to receiving nivolumab
• Recursive partitioning analysis (RPA) class III patients defined as those expected to begin reirradiation within 2 years of first course of radiation therapy AND are percutaneous endoscopic gastrostomy (PEG) dependent or have a tracheostomy (patients who have undergone total laryngectomy are not excluded)
• Patients with metastases
• Prior treatment with a programmed cell death protein-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor
• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment
• Patients with primary salivary gland cancers are excluded
• Patients who have had chemotherapy or biological therapy within 4 weeks of registration
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, autoimmune disease requiring systemic steroids, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who are pregnant or breast-feeding
• Patients with known active human immunodeficiency virus (HIV), hepatitis (hep) B, or hep C infection
• Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (nivolumab, IMRT); Patients receive nivolumab IV over 30 minutes on weeks -2, 0, 2, 4, and 6 and undergo IMRT once daily beginning on week 0 for up to 6-6.5 weeks. Beginning week 10, patients receive nivolumab IV over 30 minutes every 4 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.	Biological: Nivolumab; Given IV; Other Names: BMS-936558; MDX-1106; ONO-4538; Opdivo; Radiation: IMRT; Undergo intensity-modulated radiation therapy; Other Names: Intensity Modulated RT; Intensity-Modulated Radiotherapy; Intensity-Modulated Radiation Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Progression-Free Survival (PFS)	95% confidence interval will be estimated by Kaplan-Meier method for all participants.	1 year from study start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Overall Survival (OS)	Will be assessed using Kaplan-Meier method.	1 year from study start
Number of Participants With Pattern of Failure	To evaluate patterns of failure as local, regional, or distant.	1 year from study start
Number of Participants With Incidence of Acute Adverse Events	Acute toxicities will be identified and their incidence rate estimated.	Up to 1 year from study start
Number of Participants With Incidence of Late Adverse Events	Late toxicities will be identified and their incidence rate estimated.	2 years from study start
Quality of Life (QOL)	The FACT-HN (Functional Assessment of Cancer Therapy-Head and Neck) (version 4) consists of a cancer-specific questionnaire, FACT-G (Functional Assessment of Cancer Therapy - General), in addition to 12 H&N cancer-specific items (the HN subscale).The Functional Assessment of Cancer Therapy-Head and Neck Quality of Life questionnaire may be completed by the patient using paper or electronically. FACT-HN total score ranges between 0 and 148. The higher the score, the better the QOL	At baseline, end of Intensity-Modulated Radiation Therapy, and weeks 18, 30, 52, and 104, baseline and month 12

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Bristol-Myers Squibb; National Cancer Institute (NCI); The Cleveland Clinic; National Institutes of Health (NIH); Medical College of Wisconsin
• Investigators: Principal Investigator: Nabil F. Saba, MD, Emory University

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2018
• Primary Completion (Actual): July 25, 2022
• Study Completion (Actual): September 7, 2023

Study Registration Dates

• First Submitted: April 30, 2018
• First Submitted That Met QC Criteria: April 30, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 14, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Head and Neck Neoplasms; Recurrence; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: IRB00100923; P30CA138292 (U.S. NIH Grant/Contract); NCI-2018-00064 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); Winship4221-17 (Other Identifier: Emory University Hospital/Winship Cancer Institute)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No