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Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)

NCT02952586

Description:

This is a phase 3 randomized, placebo controlled study to evaluate the safety and anti-tumor activity of Avelumab in combination with standard of care chemoradiation (SoC CRT) versus SoC CRT alone in front-line treatment of patients with locally advanced head and neck cancer.

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study To Compare Avelumab In Combination With Standard of Care Chemoradiotherapy (SoC CRT) Versus SoC CRT for Definitive Treatment In Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck (JAVELIN HEAD AND NECK 100)
  • Official Title: A Randomized Double-blind Phase 3 Study Of Avelumab In Combination With Standard Of Care Chemoradiotherapy (Cisplatin Plus Definitive Radiation Therapy) Versus Standard Of Care Chemoradiotherapy In The Front-line Treatment Of Patients With Locally Advanced Squamous Cell Carcinoma Of The Head And Neck

Clinical Trial IDs

  • ORG STUDY ID: B9991016
  • SECONDARY ID: 2016-001456-21
  • SECONDARY ID: LOCALLY ADVANCED HEAD AND NECK
  • NCT ID: NCT02952586

Conditions

  • Squamous Cell Carcinoma of the Head and Neck

Interventions

DrugSynonymsArms
AvelumabAvelumab + SOC Chemoradiation Therapy

Purpose

This is a phase 3 randomized, placebo controlled study to evaluate the safety and anti-tumor activity of Avelumab in combination with standard of care chemoradiation (SoC CRT) versus SoC CRT alone in front-line treatment of patients with locally advanced head and neck cancer.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Avelumab + SOC Chemoradiation TherapyExperimentalAvelumab 10 mg/kg IV: Day 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; and Q2W for 12 months during the Maintenance Phase Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase Intensity Modulated Radiation Therapy (IMRT) 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase
  • Avelumab
    Placebo + SOC CRTPlacebo ComparatorPlacebo IV matching avelumab: Days 1 of the Lead-in Phase; Days 8, 25, and 39 of the CRT Phase; Q2W for 12 months during the Maintenance Phase Cisplatin 100 mg/m2 IV: Days 1, 22, and 43 of the CRT Phase IMRT 70 Gy/35 fractions/7 weeks; 1 fraction per day, 5 fractions/week for 7 weeks during the CRT Phase

      Eligibility Criteria

      Inclusion Criteria:

      - Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx

      - HPV negative disease, Stage III, IVa, IVb or Non oropharyngeal HPV positive disease, Stage III, IVa, IVb or HPV positive oropharyngeal disease T4, N2c, or N3

      - No prior therapy for advanced stage SCCHN; eligible for definitive CRT with curative intent.

      - Available tumor samples for submission or willing to undergo further tumor biopsies:

      - Age ≥18 years (≥19 in Korea;20 years in Japan and Taiwan).

      - ECOG Performance Status (PS) 0 or 1 (Appendix 2).

      - Adequate bone marrow function

      - Adequate renal function

      - Adequate liver function

      - Pregnancy test (for patients of childbearing potential) negative at screening

      Exclusion Criteria:

      - Prior immunotherapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways.

      - Major surgery 4 weeks prior to randomization.

      - Diagnosis of any other malignancy within 5 years prior to randomization, except for superficial esophageal cancer (TIS or T1a) fully resected by endoscopy, prostate cancer (Gleason score ≤6) either curatively treated or deemed to not require treatment, ductal in situ carcinoma of the breast that has completed curative treatment, adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or bladder.

      - Active autoimmune disease

      - Any of the following in the 6 months prior to randomization: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.

      - Active infection requiring systemic therapy.

      - Use of immunosuppressive medication at time of randomization

      - Prior organ transplantation including allogenic stem-cell transplantation.

      - Diagnosis of prior immunodeficiency or known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.

      - Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

      - Vaccination within 4 weeks prior to randomization.

      - Current use of or anticipated need for treatment with other anti-cancer drugs.

      - Pregnant female patients, breastfeeding female patients, and male patients able to father children and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in the protocol for the duration of the study and for at least 6 months after the last dose of cisplatin and 60 days after the last dose of avelumab/placebo (whichever is later).

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

      Primary Outcome Measures

      Measure:Progression Free Survival (PFS)
      Time Frame:Baseline up to 49 months
      Safety Issue:
      Description:PFS per modified Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1

      Secondary Outcome Measures

      Measure:Overall Survival (OS)
      Time Frame:Baseline up to 103 months
      Safety Issue:
      Description:
      Measure:Trough plasma concentration (Ctrough) of avelumab
      Time Frame:Lead-in Day 1; and Days 8 and 25 of CRT phase
      Safety Issue:
      Description:Ctrough is defined as the trough plasma concentration of avelumab
      Measure:Percentage of patients with positive anti-drug antibodies (ADA) and neutralizing antibodies
      Time Frame:Day 1 of the Lead-in Phase, and Days 8, and 25 of the CRT Phase
      Safety Issue:
      Description:
      Measure:Tumor tissue biomarker status
      Time Frame:Lead-in Day 1
      Safety Issue:
      Description:Tumor tissue biomarkers including, but not limited to PD-L1 expression and tumor-infiltrating CD8+ T-lymphocytes.
      Measure:Maximum plasma concentration (Cmax) of Avelumab
      Time Frame:Lead-in Day 1; and Days 8 and 25 of CRT phase
      Safety Issue:
      Description:
      Measure:Area under the concentration-time curve extrapolated to infinity (AUCinf) for cisplatin
      Time Frame:Day 1 of CRT phase
      Safety Issue:
      Description:
      Measure:Cmax of Cisplatin
      Time Frame:Day 1 of CRT phase
      Safety Issue:
      Description:
      Measure:Clearance (CL) of cisplatin
      Time Frame:Day 1 of CRT phase
      Safety Issue:
      Description:
      Measure:Time to maximum plasma concentration (Tmax) and elimination half-life (t1/2)for cisplatin
      Time Frame:Day 1 of CRT phase
      Safety Issue:
      Description:
      Measure:Volume of distribution (Vz) for cisplatin (total and free)
      Time Frame:Day 1 of CRT phase
      Safety Issue:
      Description:
      Measure:Change from Baseline in the EuroQoL Group 5-Dimension 5- Level Self-Report Questionnaire (EQ-5D-5L)
      Time Frame:Lead-in Day 1 and CRT phase Day 1 and Day 29
      Safety Issue:
      Description:
      Measure:Change from baseline in National Cancer Comprehensive Network (NCCN) Head and Neck Symptom Index-22 items (FHNSI-22)
      Time Frame:Lead-in Day 1 and CRT phase Day 1 and Day 29
      Safety Issue:
      Description:
      Measure:Rate of pathologic complete response
      Time Frame:Baseline up to 49 months
      Safety Issue:
      Description:In any patients with resected specimens, neck dissection.
      Measure:Locoregional tumor control
      Time Frame:Baseline up to 49 months
      Safety Issue:
      Description:Per modified RECIST v1.1
      Measure:Distant metastatic failure
      Time Frame:Baseline up to 49 months
      Safety Issue:
      Description:Per modified RECIST v1.1
      Measure:Objective Response Rate - Percentage of Participants With Objective Response
      Time Frame:Baseline up to 49 months
      Safety Issue:
      Description:Per modified RECIST v1.1
      Measure:Duration of response
      Time Frame:Baseline up to 49 months
      Safety Issue:
      Description:Per modified RECIST v1.1
      Measure:The incidence of pathologically-positive neck dissection versus the incidence of pathologically-negative neck dissection
      Time Frame:Baseline up to 49 months
      Safety Issue:
      Description:

      Details

      Phase:Phase 3
      Primary Purpose:Interventional
      Overall Status:Not yet recruiting
      Lead Sponsor:Pfizer

      Trial Keywords

        Last Updated

        January 5, 2017