Clinical trial NCT03521570: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Head and Neck Squamous Cell Carcinoma
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: The Cleveland Clinic
name: Medical College of Wisconsin
name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2018-05-11
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Number of Participants With Progression-Free Survival (PFS)
timeFrame: 1 year from study start
Secondary outcomes:
measure: Number of Participants With Overall Survival (OS)
timeFrame: 1 year from study start
measure: Number of Participants With Pattern of Failure
timeFrame: 1 year from study start
measure: Number of Participants With Incidence of Acute Adverse Events
timeFrame: Up to 1 year from study start
measure: Number of Participants With Incidence of Late Adverse Events
timeFrame: 2 years from study start
measure: Quality of Life (QOL)
timeFrame: At baseline, end of Intensity-Modulated Radiation Therapy, and weeks 18, 30, 52, and 104, baseline and month 12
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Emory University
name: Nabil F. Saba, MD
role: PRINCIPAL_INVESTIGATOR
References: