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

NCT03521570 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB00100923NCI-2018-00064Winship4221-17P30CA138292
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 4

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.

Conditions

Recurrent Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Number of Participants With Overall Survival (OS)

  1 year from study start

• Number of Participants With Pattern of Failure

  1 year from study start

• Number of Participants With Incidence of Acute Adverse Events

  Up to 1 year from study start

• Number of Participants With Incidence of Late Adverse Events

  2 years from study start

• Quality of Life (QOL)

  At baseline, end of Intensity-Modulated Radiation Therapy, and weeks 18, 30, 52, and 104, baseline and month 12

Study Arms (1)

Treatment (nivolumab, IMRT)

EXPERIMENTAL

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.

Radiation: IMRT; Biological: Nivolumab

Interventions

IMRT RADIATION

Undergo intensity-modulated radiation therapy

Also known as: Intensity-Modulated Radiation Therapy, Intensity Modulated RT, Intensity-Modulated Radiotherapy

Treatment (nivolumab, IMRT)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, ONO-4538, Opdivo

Treatment (nivolumab, IMRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Emory University: lead
• Bristol-Myers Squibb: collaborator
• The Cleveland Clinic: collaborator
• Medical College of Wisconsin: collaborator
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 38780927 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy, Intensity-Modulated; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Nabil F. Saba MD, FACP
• Organization: Emory University

nfsaba@emory.edu

404-778-0278

Study Officials

• Nabil F. Saba, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: May 11, 2018
• Study Start: June 28, 2018
• Primary Completion: July 25, 2022
• Study Completion: September 7, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Locations

US (4)