Clinical Trials /

Preoperative Immune Checkpoint Inhibitor for Patients With Primary Untreated or Recurrent/Metastatic SCCHN

NCT03878979

Description:

Nivolumab (also known as BMS-936558) before surgery to people with newly diagnosed or recurrent squamous cell carcinoma of head and neck (SCCHN).

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Preoperative Immune Checkpoint Inhibitor for Patients With Recurrent or Metastatic SCCHN Undergoing Surgical Salvage
  • Official Title: Preoperative Immune Checkpoint Inhibitor for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck Undergoing Surgical Salvage

Clinical Trial IDs

  • ORG STUDY ID: J1923
  • SECONDARY ID: IRB00207577
  • SECONDARY ID: CA209-9H7
  • NCT ID: NCT03878979

Conditions

  • Head and Neck Squamous Cell Carcinoma
  • Head and Neck Cancer
  • Head and Neck Cancer Metastatic

Interventions

DrugSynonymsArms
Nivolumab 480mg and surgical resectionOpdivo, ONO-4538, BMS-936558, MDX 1106Newly diagnosed SCCHN

Purpose

Nivolumab (also known as BMS-936558) before surgery to people with newly diagnosed or recurrent squamous cell carcinoma of head and neck (SCCHN).

Detailed Description

      This research is being done to see if it is safe and feasible to give the investigational
      drugs, nivolumab (also known as BMS-936558) before surgery to people with newly diagnosed or
      recurrent squamous cell carcinoma of head and neck (SCCHN). Patients with recurrent disease
      may have a limited number of sites of metastatic (spread) squamous cell carcinoma of head and
      neck. Another goal of this study is to learn how nivolumab impacts the immune system's
      ability to treat the cancer. While nivolumab is approved by the U. S. Food and Drug
      Administration (FDA) for the treatment of patients with metastatic SCCHN with progression on
      or after platinum-based chemotherapy, the word "investigational" in this context means that
      the study drugs are not approved by the FDA for the treatment of head and neck cancers prior
      to surgery and thus is still being tested in research studies. However, the FDA is allowing
      the use of nivolumab in this study.

      This study will have two arms. Cohort (arm) 1 will examine one dose of nivolumab given about
      4 weeks before surgical resection (removal) of a newly diagnosed SCCHN. Twelve patients will
      be enrolled to this arm. Cohort 2 will examine one dose of nivolumab given about 4 weeks
      before surgical resection (removal) of SCCHN which has recurred and possibly spread to
      distant sites, but still can be resected with one surgery. Twelve patients will be enrolled
      to this arm.
    

Trial Arms

NameTypeDescriptionInterventions
Newly diagnosed SCCHNExperimentalOne dose of nivolumab given about 4 weeks before surgical resection (removal) of a newly diagnosed SCCHN.
  • Nivolumab 480mg and surgical resection
Reccurence of SCCHNExperimentalOne dose of nivolumab given about 4 weeks before surgical resection (removal) of SCCHN which has recurred.
  • Nivolumab 480mg and surgical resection

Eligibility Criteria

        Inclusion:

        Cohort 1: Subjects must have histologically confirmed previously untreated locally advanced
        squamous cell carcinoma of the head and neck which is amenable to surgical resection

        Cohort 2: Subjects must have histologically confirmed recurrent squamous cell carcinoma of
        head and neck, which is amenable for salvage surgery. Sites of recurrence may either be
        locoregional or distant (non-CNS site) if resection can be done in one surgical field.

          -  The primary site should be oral cavity, oropharynx, hypopharynx, or larynx. Squamous
             cell carcinoma of unknown primary, diagnosed in lymph nodes in neck, can be included
             but should be tested for HPV by DNA or RNA in situ hybridization (ISH).

          -  Subjects must have confirmation of HPV status by DNA or RNA ISH if the primary site is
             oropharynx.

          -  Subjects must have at least one lesion that can be biopsied at baseline.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

          -  Age >18 years.

          -  Life expectancy of greater than 6 months.

          -  Patients must have normal organ and marrow function as defined below:

               -  leukocytes ≥ 1,500/mcL

               -  absolute neutrophil count ≥ 1,000/mcL

               -  platelets ≥ 100,000/mcL

               -  total bilirubin ≤ 1.5 X institutional upper limit of normal (except subjects with
                  Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL)

               -  AST(SGOT)/ALT(SGPT) ≤ 3 X institutional upper limit of normal

               -  Creatinine OR creatinine clearance within normal institutional limits OR ≥ 40
                  mL/min (using modified Cockcroft-Gault formula) for patients with creatinine
                  levels above institutional normal.

          -  Resting and walking O2 saturation must remain above 90% at the time of screening

          -  Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
             the start of study treatment.

          -  Women must not be breastfeeding

          -  Women of childbearing potential (WOCBP) must agree to follow instructions for
             method(s) of contraception for the duration of treatment with study treatment and for
             5 months post-treatment completion. Women should use an adequate method(s) of
             contraception (Refer to nivolumab IB for WOCBP and methods of contraception to be
             provided)

          -  Males who are sexually active with WOCBP must agree to follow instructions for
             method(s) of contraception (Refer to protocol appendix E) for the duration of
             treatment with study treatment(s) and 7 months post-treatment completion. In addition,
             male participants must be willing to refrain from sperm donation during this time. Men
             who are sexually active with WOCBP must agree to follow instructions for method(s) of
             contraception

          -  Patient understands the study regimen, its requirements, risks and discomforts and is
             able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC
             approved written informed consent form in accordance with regulatory and institutional
             guidelines must be obtained before the performance of any protocol related procedures
             that are not part of normal patient care. Subjects must be competent to report AEs,
             understand the drug dosing schedule and use of medications to control AEs.

        Exclusion Criteria

          -  Any active history of a known autoimmune disease. Subjects with vitiligo, type 1
             diabetes mellitus, residual hypothyroidism requiring hormone replacement, or
             conditions not expected to recur in the absence of an external trigger are permitted
             to enroll.

          -  Patients who have had prior chemotherapy for newly diagnosed (cohort 1) or recurrent
             (cohort 2) head and neck cancer. In cohort 2 only, previous perioperative chemotherapy
             or chemoradiation for the management of localized or locally advanced disease
             permitted.

          -  Patients who had prior surgical resection of distant metastasis (metastatectomy)
             within 6 months of enrollment.

          -  Patients who received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti
             CD137, anti-CTLA-4 antibody therapies, any other antibody or drug specifically
             targeting T-cell co-stimulation or checkpoint pathways. Any live / attenuated vaccine
             (eg varicella, zoster, yellow fever, rotavirus, oral polio and measles, mumps, rubella
             (MMR)) during treatment and until 100 days post last dose.

          -  Patients with uncontrolled brain metastases

          -  Patients with brain metastases must have stable neurologic status following local
             therapy (surgery or radiation) for at least 2 weeks without the use of steroids or on
             stable or decreasing dose of < 10mg daily prednisone (or equivalent), and must be
             without neurologic dysfunction that would confound the evaluation of neurologic and
             other adverse events. Patients with a history of carcinomatous meningitis are not
             eligible.

          -  Patients who have an active concurrent malignancy. Patients with localized cutaneous
             squamous cell carcinoma or basal cell carcinoma which is completely excised are
             allowed to enroll.

          -  Uncontrolled inter-current illness including, but not limited to, ongoing or active
             infection, administration of live vaccination in the prior 3 months, symptomatic
             congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia,
             myocardial infarction or new onset angina within six months of enrollment, or
             psychiatric illness/social situations that would limit compliance with study
             requirements.

          -  Women who are pregnant or nursing.

          -  Men with female partners who are not willing to use contraception.

          -  Active infection with hepatitis B or hepatitis C defined as positive tests for
             hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA).

          -  Patients with a condition requiring systemic treatment with either corticosteroids
             (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
             days of randomization. Inhaled or topical steroids and adrenal replacement steroid
             doses < 10 mg daily prednisone equivalent, are permitted in the absence of active
             autoimmune disease.

          -  Patients with nasopharynx carcinoma

          -  Patient with HIV are excluded given the unknown risk of interaction with HAART and the
             unknown benefit of immunotherapy in this population.

          -  Participants who have received a live / attenuated vaccine within 30 days of first
             treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety as measured by number of participants with drug-related adverse events
Time Frame:Up to 100 days after the last dose of nivolumab or 30 days after surgery (whichever is longer)
Safety Issue:
Description:Safety of neoadjuvant nivolumab administration in patients with newly diagnosed head and neck cancer and those with locoregional recurrence or oligometastatic disease undergoing surgical resection measured by number of participants with drug related adverse events as defined by CTCAE v5.0, occurring up to 100 days after the last dose of nivolumab or 30 days after surgery (whichever is longer)

Secondary Outcome Measures

Measure:Major pathologic response rate
Time Frame:Day 0 (after surgery)
Safety Issue:
Description:Number of participants with < 10% residual tumor in the resection specimen.
Measure:Progression free survival (PFS)
Time Frame:up to 3 years
Safety Issue:
Description:Number of months until radiologic or clinical progression or death, whichever occurs first.
Measure:Radiographic response rate
Time Frame:up to 4 weeks post-intervention
Safety Issue:
Description:Number of participants with response as determined by RECIST version 1.1 and immune-related response criteria (irRC). Per RECIST criteria, Complete response (CR) is a disappearance of all target lesions, Partial response (PR) is >= 30% decrease in the sum of the largest diameter (LD) of target lesions, Progressive disease (PD) is >= 20% increase in the sum of the LD of target lesions. Per irRC, immune-related Complete Response (irCR) is the disappearance of all lesions, measured or unmeasured, and no new lesions; an immune-related Partial Response (irPR) is a 50% drop in tumour burden from baseline as defined by the irRC; and immune-related Progressive Disease (irPD) is a 25% increase in tumour burden from the lowest level recorded.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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