Clinical Trials /

Feasibility and Tolerance of Nivolumab Neoadjuvant Immunotherapy in High Risk HPV Driven Oropharynx Cancer

NCT03838263

Description:

The aim of this research is to study the feasibility of neoadjuvant treatment before chemoradiation in "high risk" HPV-driven Oropharynx cancer

Related Conditions:
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Feasibility and Tolerance of Nivolumab Neoadjuvant Immunotherapy in High Risk HPV Driven Oropharynx Cancer
  • Official Title: A Multicenter, Randomized, Open Label, Phase II Study Evaluating the Feasibility and Tolerance of Nivolumab Neoadjuvant Immunotherapy in High Risk HPV Driven Oropharynx Cancer

Clinical Trial IDs

  • ORG STUDY ID: UC-0130/1804
  • SECONDARY ID: 2018-000626-60
  • NCT ID: NCT03838263

Conditions

  • Oropharynx Cancer

Interventions

DrugSynonymsArms
NivolumabExperimental arm

Purpose

The aim of this research is to study the feasibility of neoadjuvant treatment before chemoradiation in "high risk" HPV-driven Oropharynx cancer

Detailed Description

      Methodology:

      Patient screened wil be randomized 2:1 between 2 arms:

        -  Experimental arm: Nivolumab 2 infusions (2 weeks part) before standard of care
           chemoradiation for 7 weeks with Cisplatin at week 1, 4, and 7

        -  Control arm: Standard of care chemoradiation for 7 weeks with Cisplatin at week 1, 4,
           and 7

      Primary Objective:

      To assess the feasibility and tolerance of neoadjuvant nivolumab treatment before
      chemoradiation in "high risk" HPV-driven Oropharynx Cancer
    

Trial Arms

NameTypeDescriptionInterventions
Experimental armExperimentalExperimental arm with Nivolumab 2 infusions (2 weeks apart) before Standard of Care chemoradiation for 7 weeks with high-dose cisplatin (100mg/m2) at week 1, 4 and 7
  • Nivolumab
Control armActive ComparatorControl arm: Standard of Care chemoradiation for 7 weeks with high-dose cisplatin (100mg/m2) at week 1, 4 and 7

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Age ≥18 years old
    
              2. Histologically confirmed HPV-positive Oropharyngeal squamous cell carcinoma (OPSCC)
                 amenable to curative treatment with RT-CT.
    
                 (HPV status is defined on the basis of the combination of 2 assays: p16 protein
                 overexpression assessed by immunohistochemistry (IHC) and high-risk HPV DNA
                 identification by in-situ Hybridization (ISH) or PCR. An HPV-driven OPSCC is defined
                 as a tumor that is positive for both p16 IHC and HPV-DNA ISH or PCR)
    
              3. According to the 8th TNM edition, eligible stages are as follow:
    
                   -  Irrespective of tobacco consumption: Stage T4 (any N), N2 or N3 (any T)
    
                   -  Only if tobacco consumption ≥10 pack- years: T1-3N1 and T3N0 (T1N0 and T2N0
                      irrespective of tobacco consumption are not eligible for the study)
    
              4. Planned date of chemoradiation allowing 2 treatment infusions, 2 weeks apart
    
              5. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
    
              6. Screening laboratory values must meet the following criteria (using CTCAE v5.0) and
                 should be obtained within 7 days prior to the randomisation:
    
                   1. Polynuclear neutrophils ≥1.5 x 10⁹/L
    
                   2. Platelets ≥100 x 10⁹/L
    
                   3. Hemoglobin ≥9.0 g/dL
    
                   4. Alanine aminotransferase (ALAT)/aspartate transaminase (ASAT) ≤ 2.5 x upper limit
                      of normal (ULN)
    
                   5. Total Bilirubin ≤1.5 x ULN (except Gilbert Syndrome : <3.0 mg/dL)
    
                   6. Creatinine clearance ≥60 mL/min (measured or calculated by Cockcroft and Gault
                      formula)
    
              7. Potentially reproductive patients must agree to use a highly effective contraceptive
                 method while on treatment and up to 6 months after the end of chemoradiation
    
              8. Women of childbearing potential must have a negative serum or urine pregnancy test
                 done within 72 hours before randomisation
    
              9. Patients must be willing and able to comply with scheduled visits, treatment plan,
                 laboratory tests and other study procedures (including mandatory study-specific
                 biopsies)
    
             10. Subjects must have at least one lesion amenable to biopsy
    
             11. Subjects must have at least one measurable lesion (different from the lesion amenable
                 to biopsy) as per RECIST 1.1 criteria to assess efficacy
    
             12. Consent to provide archived tumour tissue sample, if available
    
             13. Patients must be affiliated to a Social Security System
    
             14. Patient information and written informed consent form signed
    
            Exclusion Criteria:
    
              1. Prior treatment for OPSCC
    
              2. Prior treatment with anti PD-1/PD-L1 and CTLA-4
    
              3. Distant metastases
    
              4. Tumour embolization within 28 days prior to the first dose of study drug.
    
              5. Contra-indication(s) to receive high-dose cisplatin as listed in the most updated
                 Summary of Product Characteristics (including creatinine clearance <60 mL/min,
                 pre-existing hearing loss or neurological disorder)
    
              6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
                 infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
                 angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, or
                 psychiatric illness and social situations that would limit compliance with study
                 requirement or compromise the ability of the subject to give written informed consent
    
              7. Current or prior use of immunosuppressive medication within 14 days before the first
                 dose, including intranasal and inhaled corticosteroids or systemic corticosteroids
    
              8. Active or prior documented autoimmune or inflammatory disease within the 2 years prior
                 to start of treatment (including inflammatory bowel disease [e.g., ulcerative colitis,
                 Crohn's disease], celiac disease, irritable bowel disease, or other serious chronic
                 gastrointestinal conditions associated with diarrhea; systemic lupus erythematosus;
                 Wegener syndrome [granulomatosis with polyangiitis]; myasthenia gravis; Graves'
                 disease; rheumatoid arthritis; hypophysitis, uveitis, etc.) The following are
                 exceptions to these criteria:a) Subjects with vitiligo or alopecia, b) Subjects with
                 hypothyroidism (e.g.,Hashimoto syndrome) stable on hormone replacement and c) Subjects
                 with psoriasis not requiring systemic treatment (within the past 2 years)
    
              9. History of primary immunodeficiency or organ transplant requiring immunosuppressive
                 drugs
    
             10. Patients with a known HIV, active hepatitis B or C infection
    
             11. Other invasive malignancy within 3 years except for noninvasive malignancies such as
                 cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma
                 in situ of the breast that has/have been surgically cured
    
             12. Pregnant women or women who are breast-feeding
    
             13. Patients with any psychological, familial, sociological or geographical condition
                 potentially hampering compliance with the study protocol and follow-up schedule; those
                 conditions should be discussed with the patient before registration in the study
    
             14. Individuals deprived of liberty or placed under the authority of a tutor
    
             15. Severe infection requiring parenteral antibiotics treatment
    
             16. Known history or active symptomatic interstitial lung disease
    
             17. Patients with major surgery within 28 days, or open biopsy within 7 days, prior to
                 randomisation. Patients must have recovered from major side effects of the surgery
                 before randomisation
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:The rate of patients that fulfill the 3 or 5 conditions as described below (Feasibility assessment of nivolumab neoadjuvant treatment before chemoradiation)
    Time Frame:Between baseline and until 3 months (at the end of chemoradiation)
    Safety Issue:
    Description:the rate of patients : (1) who can receive the 2 nivolumab infusions planned at D1 and between D14 to D16 among patients in the experimental arm And (2) who can receive chemoradiation at D30 (-2 /+7) after the second nivolumab infusion, without delay of more than 7 days with respect to the planned start of chemoradiation (RT-CT) among patients in the experimental arm And (3) with no radiotherapy break of one week or more, among patients in the experimental arm and patients in the control arm separately And (4) with minimal dose of radiotherapy (dose received >95% of theoretical dose) among patients in the experimental arm and patients in the control arm separately And (5) with minimal dose of chemotherapy of ≥200 mg/m² of cisplatin (CDDP) among patients in the experimental arm and patients in the control arm separately

    Secondary Outcome Measures

    Measure:The incidence of Adverse Events related or not related to chemoradiation and Nivolumab
    Time Frame:During treatment phase and until 90 days after the last fraction of radiotherapy
    Safety Issue:
    Description:Acute and delayed toxicities assessed according to national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0
    Measure:Objective Response Rate in the experimental arm
    Time Frame:Between baseline and up to 17 days after the second infusion of nivolumab
    Safety Issue:
    Description:Radiological response will be assessed according to RECIST 1.1.
    Measure:Tumor Response in both arms
    Time Frame:Between baseline and 3 months after the end of chemoradiation
    Safety Issue:
    Description:Radiological response will be assessed according to RECIST 1.1.
    Measure:Overall Survival (OS)
    Time Frame:Between baseline and 2 years after the end of chemoradiation
    Safety Issue:
    Description:the time from randomization to death from any cause
    Measure:Locoregional control (LRC)
    Time Frame:Between baseline and 2 years after the end of chemoradiation
    Safety Issue:
    Description:the absence of disease progression (radiological progression according to RECIST 1.1 or clinical progression) or recurrence at the site of the primary tumor and loco-regional lymph nodes.
    Measure:Progression-Free Survival (PFS)
    Time Frame:Between baseline and 2 years after the end of chemoradiation
    Safety Issue:
    Description:The time from randomization to progression or death from any cause
    Measure:Objective Response Rate in the experimental arm
    Time Frame:Between baseline and up to 17 days after the second infusion of nivolumab
    Safety Issue:
    Description:Standardized uptake value (SUV) evolution will be assessed by positron emission tomography (PET)-scan.
    Measure:Tumor Response in both arms
    Time Frame:Between baseline and 3 months after the end of chemoradiation
    Safety Issue:
    Description:SUV evolution will be assessed by PET-scan.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:UNICANCER

    Trial Keywords

    • Nivolumab
    • High-risk
    • HPV-driven oropharynx cancer

    Last Updated