Clinical Trials /

Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy

NCT03700905

Description:

Multicenter randomized controlled phase III study of nivolumab alone or in combination with ipilimumab as immunotherapy vs standard follow-up in surgical resectable HNSCC after adjuvant therapy

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy
  • Official Title: Multicenter Randomized Controlled Phase III Study of Nivolumab Alone or in Combination With Ipilimumab as Immunotherapy vs Standard Follow-up in Surgical Resectable HNSCC After Adjuvant Therapy

Clinical Trial IDs

  • ORG STUDY ID: CA209-934
  • NCT ID: NCT03700905

Conditions

  • Head and Neck Cancer

Interventions

DrugSynonymsArms
Neoadjuvant NivolumabNeoadjuvant/adjuvant Nivolumab and Ipilimumab
Adjuvant NivolumabNeoadjuvant/adjuvant Nivolumab and Ipilimumab
Adjuvant Nivolumab and IpilimumabNeoadjuvant/adjuvant Nivolumab and Ipilimumab

Purpose

Multicenter randomized controlled phase III study of nivolumab alone or in combination with ipilimumab as immunotherapy vs standard follow-up in surgical resectable HNSCC after adjuvant therapy

Detailed Description

      Surgically treated locally advanced head and neck squamous cell carcinoma often requires
      postoperative chemoradiation with high risk of acute and late toxicity. DFS after 2 years is
      approximately 70%. Combining anti-PD-1 and anti-CTLA4 as a maintenance therapy may improve
      DFS due to anti-tumor effects of immunotherapy by enhancing cross-presentation of tumor
      antigens.
    

Trial Arms

NameTypeDescriptionInterventions
Neoadjuvant/adjuvant Nivolumab and IpilimumabExperimentalNeoadjuvant dose with Nivolumab 3mg/kg after randomization within 2 weeks before surgery Surgical resection of primary tumor including neck dissection according to standard of care 6-7 weeks risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43, or Cisplatin once weekly (40mg/m2) for high risk patients only), start within 6 weeks post-surgery Arm Ia: • Adjuvant administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months Arm Ib: • Adjuvant administration of Nivolumab 3mg/kg i.v. d1 every 2 weeks and Ipilimumab 1mg/kg i.v. d1 every 6 weeks within 6 weeks after end of radiotherapy until progression or up to 6 months
  • Neoadjuvant Nivolumab
  • Adjuvant Nivolumab
  • Adjuvant Nivolumab and Ipilimumab
Surgical resection + adjuvant radio(-chemo)therapyActive ComparatorSurgical resection of primary tumor including neck dissection according to standard of care 6-7 weeks risk-adapted adjuvant radio(-chemo)therapy 56-66 Gy (chemotherapy Cisplatin 100 mg/m2 on days 1, 22, 43 or Cisplatin once weekly (40mg/m2) in high risk patients), start within 6 weeks post-surgery Standard follow-up

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Histologically proven SCC of the oropharynx, oral cavity, hypopharynx, and larynx (not
                 older than 3 months before randomization)
    
              -  clinical stage III-IVB (T1, N2-3; T2, N2-3; T3, N0-3; T4a, N0-3)
    
              -  Oropharyngeal cancer HPV-negative (p16 immunohistochemistry negative)
    
              -  Primary tumor and neck metastasis must be resectable
    
              -  Written and signed informed consent
    
              -  Performance Status of 0 or 1 using ECOG
    
              -  Male and female with age ≥ 18
    
              -  Curative treatment intent (cM0)
    
              -  Screening laboratory values must meet the following criteria and should be obtained
                 within 4 weeks prior to randomization
    
                   -  WBC ≥ 2000/μL
    
                   -  Neutrophils ≥ 1500/μL
    
                   -  Platelets ≥ 100 x103/μL
    
                   -  Hemoglobin > 9.0 g/dL
    
                   -  Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using
                      the Cockcroft-Gault formula below):
    
                   -  Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in
                      mg/dL
    
                   -  Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in
                      mg/dL
    
                   -  AST/ALT ≤ 3 x ULN
    
                   -  Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have
                      total bilirubin < 3.0 mg/dL)
    
              -  Women of childbearing potential (WOCBP)1 must use appropriate method(s) of
                 contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30
                 days plus the time required for nivolumab to undergo five half-lives) after the last
                 dose of investigational drug
    
              -  WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
                 or equivalent units of HCG) within 24 hours prior to the start of nivolumab.
    
              -  Women must not be breastfeeding
    
              -  Men who are sexually active with WOCBP must use any contraceptive method with a
                 failure rate of less than 1% per year. Men receiving nivolumab and who are sexually
                 active with WOCBP will be instructed to adhere to contraception for a period of 31
                 weeks after the last dose of investigational product.
    
            Exclusion Criteria:
    
              -  Patients should be excluded if they have an active, known or suspected autoimmune
                 disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes
                 mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone
                 replacement, psoriasis not requiring systemic treatment, or conditions not expected to
                 recur in the absence of an external trigger
    
              -  Patients should be excluded if they have 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.
    
              -  As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab
                 combinations, drugs with a predisposition to hepatoxicity should be used with caution
                 in patients treated with nivolumab-containing regimen.
    
              -  Patients should be excluded if they have had prior treatment with an anti-PD-1,
                 anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug
                 specifically targeting T-cell costimulation or immune checkpoint pathways
    
              -  Prior invasive malignancy except controlled skin cancer or carcinoma in situ of cervix
    
              -  Unknown primary (CUP), nasopharyngeal or salivary gland cancer
    
              -  Distant metastatic disease or adenopathy below the clavicles
    
              -  Serious co-morbidity, e.g. high-grade carotid artery stenosis, congestive heart
                 failure NYHA grade 3 and 4, liver cirrhosis CHILD C. If clinically suspected, further
                 diagnostic is indicated according to the judgement of the investigator.
    
              -  Pregnancy or lactation
    
              -  Women of child-bearing potential with unclear contraception
    
              -  Previous treatment for the study cancer with chemotherapy, radiotherapy,
                 EGFR-targeting agents or surgery exceeding biopsy in head and neck
    
              -  Prior radiotherapy to the region of the study cancer that would result in overlap of
                 radiation therapy fields
    
              -  Concurrent treatment with other experimental drugs or participation in another
                 clinical trial with any investigational drug within 30 days prior to study screening
    
              -  Patients should be excluded if they are positive test for hepatitis B virus surface
                 antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating
                 acute or chronic infection
    
              -  Patients should be excluded if they have known history of testing positive for human
                 immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
    
              -  Allergies and Adverse Drug Reaction: History of severe hypersensitivity reaction to
                 any monoclonal antibody
    
              -  History of allergy to study drug components
    
              -  Social situations that limit compliance with study requirements or patients with an
                 unstable condition (e.g., psychiatric disorder, a recent history of drug or alcohol
                 abuse, interfering with study compliance, within 6 months prior to screening) or
                 otherwise thought to be unreliable or incapable of complying with the requirements of
                 the protocol
    
              -  Patients institutionalized by official means or court order
    
              -  Deficient dental preservation status or not accomplished wound healing
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Disease Free Survival
    Time Frame:approximately 71 months
    Safety Issue:
    Description:disease free survival (DFS) at 3 years of nivolumab alone or in combination with ipilimumab as adjuvant immunotherapy after adjuvant radio(chemo)therapy in locally advanced resected HNSCC

    Secondary Outcome Measures

    Measure:Local regional control (LRC)
    Time Frame:Time from randomization to date of first observed histologically proven or death, up to 36 month
    Safety Issue:
    Description:Disease assessment (CT/ MRI) and Panendoscopy and FFPE in case of suspicion or recurrence
    Measure:Distant metastasis free survival (DMFS)
    Time Frame:Time from randomization to date of first observed histologically proven or death, up to 36 month
    Safety Issue:
    Description:Disease assessment (CT/ MRI)
    Measure:Overall survival (OS)
    Time Frame:until end of study (36 months after end of therapy of the last patient), approximately 71 months
    Safety Issue:
    Description:Follow Up- Visits after end of treatment every 3 months until month 36 after randomization, afterwards every 6 months
    Measure:Acute toxicity and late morbidity
    Time Frame:AEs/SAEs should be collected continuously until 12 months after randomization
    Safety Issue:
    Description:Adverse Events Assessment
    Measure:Quality of life (QoL): QLQ-C30
    Time Frame:through study completion, an average of 3 years
    Safety Issue:
    Description:Questionaire EORTC QLQ-C30
    Measure:Quality of life (QoL): Questionnaire H&N43
    Time Frame:through study completion, an average of 3 years
    Safety Issue:
    Description:Questionnaire H&N43
    Measure:Comparison of nivolumab alone group vs control and nivolumab & ipilimumab group vs control in terms of DFS
    Time Frame:assessed up to 36 month
    Safety Issue:
    Description:We compare disease free survival, defined as time from randomization to date of first observed either histologically proven recurrence (local, locoregional or distant), or death from any cause whatever occurs first, of arm Ia to arm II and of arm Ib to arm II
    Measure:Survival depending on PD-L1 Status
    Time Frame:after surgery, up to 4 weeks after surgery
    Safety Issue:
    Description:Assessment of PD-L1 Status

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Universitätsklinikum Hamburg-Eppendorf

    Last Updated