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

NCT ID: NCT03521570

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-28
• Study Completion Date: 2023-09-07

Brief 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.

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.

Conditions

Recurrent Head and Neck Squamous Cell Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

IMRT

Intervention Type: RADIATION

Undergo intensity-modulated radiation therapy

Nivolumab

Intervention Type: BIOLOGICAL

Given IV

Interventions

IMRT

Undergo intensity-modulated radiation therapy

Intervention Type: RADIATION

Nivolumab

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

Intensity-Modulated Radiation Therapy; Intensity Modulated RT; Intensity-Modulated Radiotherapy; BMS-936558; MDX-1106; ONO-4538; Opdivo

Eligibility Criteria

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

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Nabil F. Saba

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nabil F. Saba, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

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, United States

Countries

United States

References

Saba NF, Wong SJ, Nasti T, McCook-Veal AA, McDonald MW, Stokes WA, Anderson AM, Ekpenyong A, Rupji M, Abousaud M, Rudra S, Bates JE, Remick JS, Joshi NP, Woody NM, Awan M, Geiger JL, Shreenivas A, Samsa J, Ward MC, Schmitt NC, Patel MR, Higgins KA, Teng Y, Steuer CE, Shin DM, Liu Y, Ahmed R, Koyfman SA. Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma: A Nonrandomized Controlled Trial. JAMA Oncol. 2024 Jul 1;10(7):896-904. doi: 10.1001/jamaoncol.2024.1143.

Reference Type: DERIVED

PMID: 38780927 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2018-00064

Identifier Type: REGISTRY

Identifier Source: secondary_id

Winship4221-17

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA138292

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00100923

Identifier Type: -

Identifier Source: org_study_id