Clinical Trials /

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

NCT03521570

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Intensity-Modulated Radiation Therapy & Nivolumab for Recurrent or Second Primary Head & Neck Squamous Cell Cancer
  • 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 IDs

  • ORG STUDY ID: IRB00100923
  • SECONDARY ID: NCI-2018-00064
  • SECONDARY ID: Winship4221-17
  • NCT ID: NCT03521570

Conditions

  • Recurrent Head and Neck Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, ONO-4538, OpdivoTreatment (nivolumab, IMRT)

Purpose

This phase II trial studies how well intensity-modulated radiotherapy and nivolumab work together in treating participants 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:

      Participants 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,
      participants 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, participants are followed up for 2 years from the
      beginning of radiation therapy.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab, IMRT)ExperimentalParticipants 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, participants receive nivolumab IV over 30 minutes every 4 weeks for up to 10 courses in the absence of disease progression or unacceptable toxicity.
  • Nivolumab

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

          -  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 (expected to be treated less
             than 2 years from first course of therapy and have a tracheostomy or percutaneous
             endoscopic gastrostomy [PEG] tube at presentation)

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:1 year progression-free survival (PFS)
Time Frame:1 year from study start
Safety Issue:
Description:95% confidence interval will be estimated by Kaplan-Meier method for all participants.

Secondary Outcome Measures

Measure:1 year overall survival (OS)
Time Frame:1 year from study start
Safety Issue:
Description:Will be assessed using Kaplan-Meier method.
Measure:Pattern of failure
Time Frame:1 year from study start
Safety Issue:
Description:To evaluate patterns of failure as local, regional, or distant.
Measure:Incidence of acute adverse events
Time Frame:Up to 1 year from study start
Safety Issue:
Description:Acute toxicities will be identified and their incidence rate estimated.
Measure:Incidence of late adverse events
Time Frame:2 years from study start
Safety Issue:
Description:Late toxicities will be identified and their incidence rate estimated.
Measure:Quality of life (QOL)
Time Frame:Up to 2 years from study start
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Emory University

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