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

Recurrent Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03521570
• Other study ID #: IRB00100923
• Secondary ID: NCI-2018-00064Wi
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 28, 2018
• Est. completion date: December 7, 2024

Study information

• Verified date: May 2023
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 51
• Est. completion date: December 7, 2024
• Est. primary completion date: December 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Neoplasms, Squamous Cell
• Recurrence
• Recurrent Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Radiation:
• IMRT
Undergo intensity-modulated radiation therapy

Biological:
• Nivolumab
Given IV

Locations

Country	Name	City	State
United States	Emory University Hospital Midtown	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	Georgia
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin

Sponsors (6)

Lead Sponsor	Collaborator
Emory University	Bristol-Myers Squibb, Medical College of Wisconsin, National Cancer Institute (NCI), National Institutes of Health (NIH), The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1 year progression-free survival (PFS)	95% confidence interval will be estimated by Kaplan-Meier method for all participants.	1 year from study start
Secondary	1 year overall survival (OS)	Will be assessed using Kaplan-Meier method.	1 year from study start
Secondary	Pattern of failure	To evaluate patterns of failure as local, regional, or distant.	1 year from study start
Secondary	Incidence of acute adverse events	Acute toxicities will be identified and their incidence rate estimated.	Up to 1 year from study start
Secondary	Incidence of late adverse events	Late toxicities will be identified and their incidence rate estimated.	2 years from study start
Secondary	Quality of life (QOL)	The Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) Quality of Life (QOL) assessments will be performed at baseline, end of IMRT, and weeks 18, 30, 52, and 104. Paper or electronic questionnaires may be completed by the patient.	Up to 2 years from study start