Clinical Trials /

Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer

NCT02369874

Description:

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus SoC therapy in the target patient population.

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Study of MEDI4736 Monotherapy and in Combination With <span class="go-doc-concept go-doc-intervention">Tremelimumab</span> Versus Standard of Care Therapy in Patients With Head and Neck <span class="go-doc-concept go-doc-disease">Cancer</span>

Title

  • Brief Title: Study of MEDI4736 Monotherapy and in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Head and Neck Cancer
  • Official Title: A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 Monotherapy and MEDI4736 in Combination With Tremelimumab Versus Standard of Care Therapy in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
  • Clinical Trial IDs

    NCT ID: NCT02369874

    ORG ID: D4193C00002

    Trial Conditions

    Recurrent or Metastatic PD-L1-positive or -Negative Squamous Cell Carcinoma of the Head and Neck (SCCHN).

    Trial Interventions

    Drug Synonyms Arms
    MEDI4736 MEDI4736
    MEDI4736 + Tremelimumab MEDI4736 + Tremelimumab
    Standard of Care Standard of Care

    Trial Purpose

    This is a randomized, open-label, multi-center, global, Phase III study to determine the
    efficacy and safety of MEDI4736 as monotherapy and MEDI4736 + tremelimumab combination
    therapy versus SoC therapy in the target patient population.

    Detailed Description

    This is a randomized, open-label, multi-center, global, Phase III study to determine the
    efficacy and safety of MEDI4736 as monotherapy and MEDI4736 + tremelimumab combination
    therapy versus SoC therapy in the target patient population.

    The main objectives of the study are:

    - To assess the efficacy of MEDI4736 monotherapy versus SoC in patients with programmed
    cell death ligand 1 (PD-L1)-positive squamous cell carcinoma of the head and neck
    (SCCHN), in terms of progression-free survival (PFS) and overall survival (OS)

    - To assess the efficacy of MEDI4736 + tremelimumab versus SoC in patients with
    PD-L1-positive and -negative SCCHN (ie, all-comers), in terms of PFS and OS.

    Patients will undergo a pre-screening assessment on their tumor tissue sample to determine
    PD-L1 expression per a pre-specified cut-off level. Patients with 25% of tumor cells with
    membrane staining will be considered PD-L1 positive while those with 0% to 24% of tumor
    cells with membrane staining will be considered PD-L1 negative. Based on the underlying
    PD-L1 status, patients will be randomized in a 1:1:1 ratio to receive treatment with
    MEDI4736 monotherapy, MEDI4736 + tremelimumab combination therapy, or SoC therapy. Patients
    who discontinue treatment in 1 treatment group may not switch to treatment in a different
    group.

    Stratification factors include PD-L1 status, human papillomavirus status and smoking status.

    Tumor assessments will be performed every 8 weeks for the first 48 weeks and then every 12
    weeks as indicated in the schedule of procedures, with categorization of objective tumor
    response by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

    Trial Arms

    Name Type Description Interventions
    MEDI4736 Experimental MEDI4736 monotherapy MEDI4736
    MEDI4736 + Tremelimumab Experimental MEDI4736 + tremelimumab combination therapy MEDI4736 + Tremelimumab
    Standard of Care Active Comparator Standard of Care Standard of Care

    Eligibility Criteria

    Inclusion Criteria: - Age 18 years; - Written informed consent obtained from the
    patient/legal representative; - Histologically confirmed recurrent or metastatic SCCHN; -
    Tumor progression or recurrence during or after treatment with 1 regimen for recurrent or
    metastatic disease that must have contained platinum or progression within 6 months from
    multimodality therapy containing platinum; - Confirmed PD-L1-positive or -negative SCCHN
    by a specified IHC assay; - WHO/Eastern Cooperative Oncology Group (ECOG) performance
    status of 0 or 1; At least 1 lesion, - Not previously irradiated; - No prior exposure to
    immune-mediated therapy; - Adequate organ and marrow function; Evidence of post-menopausal
    status or negative urinary or serum pregnancy test for female pre-menopausal patients.
    Exclusion Criteria: - Histologically confirmed squamous cell carcinoma of any other
    primary anatomic location in the head and neck; - Received more than 1 regimen for
    recurrent or metastatic disease; -Any concurrent chemotherapy, Investigational Product,
    biologic, or hormonal therapy for cancer treatment; - Receipt of any investigational
    anticancer therapy within 28 days or 5 half-lives; - Receipt of last dose of an approved
    (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs,
    etc) within 21 days prior to the first dose of study treatment; - Major surgical procedure
    within 28 days prior to the first dose of Investigational Product; - Any unresolved
    toxicity NCI CTCAE Grade 2 from previous anticancer therapy with the exception of
    alopecia, vitiligo, and the laboratory values defined in the inclusion criterion; -
    Current or prior use of immunosuppressive medication within 14 days before the first dose
    of their assigned Investigational Product; - History of allogeneic organ transplantation;
    - Active or prior documented autoimmune or inflammatory disorders; - Uncontrolled
    intercurrent illness; - Patients with a history of brain metastases, spinal cord
    compression, or leptomeningeal carcinomatosis; - Mean QT interval corrected for heart rate
    (QTc) 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction; -
    History of active primary immunodeficiency; - Known history of previous tuberculosis; -
    Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV);
    - Receipt of live, attenuated vaccine within 30 days prior to the first dose of
    Investigational Product; - Pregnant or breast-feeding female patients; - Known allergy or
    hypersensitivity to Investigational Product

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 96 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Overall survival (OS)

    Progression-free survival (PFS)

    Secondary Outcome Measures

    Objective Response Rate (ORR)

    Duration of response (DoR)

    Disease control rate (DCR)

    Proportion of patients alive and progression free at 6 months (APF6) using investigational site assessments according to RECIST 1.1

    Proportion of patients alive and progression free at 12 months (APF12) using investigational site assessments according to RECIST 1.1

    Proportion of patients alive at 12 months (OS12)

    Proportion of patients alive at 18 months (OS18)

    Proportion of patients alive at 24 months (OS24)

    Trial Keywords

    Head and Neck cancer; MEDI4736; Tremelimumab