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

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ClinicalTrials.gov Identifier: NCT03521570
Recruitment Status : Recruiting
First Posted : May 11, 2018
Last Update Posted : March 3, 2021
Sponsor:
Collaborators:
Bristol-Myers Squibb
The Cleveland Clinic
Medical College of Wisconsin
Information provided by (Responsible Party):
Nabil F. Saba, Emory University

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.

Condition or disease Intervention/treatment Phase
Recurrent Head and Neck Squamous Cell Carcinoma Radiation: IMRT Biological: Nivolumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 51 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 28, 2018
Estimated Primary Completion Date : January 19, 2022
Estimated Study Completion Date : January 19, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

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.
Radiation: IMRT
Undergo intensity-modulated radiation therapy
Other Names:
  • Intensity-Modulated Radiation Therapy
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • ONO-4538
  • Opdivo




Primary Outcome Measures :
  1. 1 year progression-free survival (PFS) [ Time Frame: 1 year from study start ]
    95% confidence interval will be estimated by Kaplan-Meier method for all participants.


Secondary Outcome Measures :
  1. 1 year overall survival (OS) [ Time Frame: 1 year from study start ]
    Will be assessed using Kaplan-Meier method.

  2. Pattern of failure [ Time Frame: 1 year from study start ]
    To evaluate patterns of failure as local, regional, or distant.

  3. Incidence of acute adverse events [ Time Frame: Up to 1 year from study start ]
    Acute toxicities will be identified and their incidence rate estimated.

  4. Incidence of late adverse events [ Time Frame: 2 years from study start ]
    Late toxicities will be identified and their incidence rate estimated.

  5. Quality of life (QOL) [ Time Frame: Up to 2 years from study start ]
    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.



Information from the National Library of Medicine

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03521570


Contacts
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Contact: Nabil F. Saba, MD 404-686-0239 nfsaba@emory.edu

Locations
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United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Allyson Anderson    404-686-0239    allyson.anderson@emory.edu   
Contact: Shraddha Dubal    404-686-3258    shraddha.dubal@emoryhealthcare.org   
Principal Investigator: Nabil F. Saba, MD         
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Erin Davis    404-778-1805    erin.t.davis@emory.edu   
Contact: Tanie Soji    404-778-4582    tanie.thambachan@emory.edu   
Principal Investigator: Nabil F. Saba, MD         
United States, Ohio
Cleveland Clinic Foundation Recruiting
Cleveland, Ohio, United States, 44195
Contact: Shlomo A. Koyfman, MD       KOYFMAS@ccf.org   
Contact: Allison Horner    216-445-6354    starka3@ccf.org   
Principal Investigator: Shlomo A. Koyfman, MD         
United States, Wisconsin
Froedtert and the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Stuart J. Wong, MD    866-680-0505    swong@mcw.edu   
Principal Investigator: Stuart J. Wong, MD         
Sponsors and Collaborators
Emory University
Bristol-Myers Squibb
The Cleveland Clinic
Medical College of Wisconsin
Investigators
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Principal Investigator: Nabil F. Saba, MD Emory University
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Responsible Party: Nabil F. Saba, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT03521570    
Other Study ID Numbers: IRB00100923
NCI-2018-00064 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Winship4221-17 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )
First Posted: May 11, 2018    Key Record Dates
Last Update Posted: March 3, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents