Clinical Trials /

Ipilimumab, Cetuximab, and Intensity-Modulated Radiation Therapy in Treating Patients With Previously Untreated Stage III-IVB Head and Neck Cancer

NCT01935921

Description:

This phase Ib trial studies the side effects and best dose of ipilimumab when given together with cetuximab and intensity-modulated radiation therapy (IMRT) in treating patients with previously untreated stage III-IVB head and neck cancer. Monoclonal antibodies, such as ipilimumab and cetuximab, may block tumor growth in different ways by targeting certain cells. Specialized radiation therapy, such as IMRT, that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Giving ipilimumab together with cetuximab and IMRT may kill more tumor cells.

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

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ipilimumab</span>, <span class="go-doc-concept go-doc-intervention">Cetuximab</span>, and Intensity-Modulated <span class="go-doc-concept go-doc-intervention">Radiation</span> Therapy in Treating Patients With Previously Untreated Stage III-IVB Head and Neck <span class="go-doc-concept go-doc-disease">Cancer</span>

Title

  • Brief Title: Ipilimumab, Cetuximab, and Intensity-Modulated Radiation Therapy in Treating Patients With Previously Untreated Stage III-IVB Head and Neck Cancer
  • Official Title: A Phase Ib Trial of Concurrent Cetuximab (ERBITUX) and Intensity Modulated Radiotherapy (IMRT) With Ipilimumab (YERVOY) in Locally Advanced Head and Neck Cancer
  • Clinical Trial IDs

    NCT ID: NCT01935921

    ORG ID: NCI-2013-00807

    NCI ID: NCI-2013-00807

    Trial Conditions

    Stage III Hypopharyngeal Squamous Cell Carcinoma

    Stage III Laryngeal Squamous Cell Carcinoma

    Stage III Oropharyngeal Squamous Cell Carcinoma

    Stage IVA Hypopharyngeal Squamous Cell Carcinoma

    Stage IVA Laryngeal Squamous Cell Carcinoma

    Stage IVA Oropharyngeal Squamous Cell Carcinoma

    Stage IVB Hypopharyngeal Squamous Cell Carcinoma

    Stage IVB Laryngeal Squamous Cell Carcinoma

    Stage IVB Oropharyngeal Squamous Cell Carcinoma

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This phase Ib trial studies the side effects and best dose of ipilimumab when given together
    with cetuximab and intensity-modulated radiation therapy (IMRT) in treating patients with
    previously untreated stage III-IVB head and neck cancer. Monoclonal antibodies, such as
    ipilimumab and cetuximab, may block tumor growth in different ways by targeting certain
    cells. Specialized radiation therapy, such as IMRT, that delivers a high dose of radiation
    directly to the tumor may kill more tumor cells and cause less damage to normal tissue.
    Giving ipilimumab together with cetuximab and IMRT may kill more tumor cells.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To identify the starting dose of ipilimumab, in combination with standard cetuximab-IMRT
    in patients with high- or intermediate-risk, locally advanced head and neck squamous cell
    carcinoma (HNSCC), for use in a future clinical efficacy trial.

    SECONDARY OBJECTIVES:

    I. To estimate the clinical response of patients with high- or intermediate-risk, locally
    advanced HNSCC treated with above regimen using Response Evaluation Criteria in Solid Tumors
    (RECIST) 1.1 criteria.

    II. To estimate the 2-year progression-free survival of patients with high- or
    intermediate-risk, locally advanced HNSCC treated with the above regimen.

    III. To investigate serum, lymphocyte and tissue biomarkers as predictors of
    progression-free survival, toxicity and other outcome parameters in patients with high- or
    intermediate-risk, locally advanced HNSCC treated with above regimen.

    IV. To estimate the association by dose-response modeling between dose of ipilimumab,
    clinical response and biomarkers.

    OUTLINE: This is a dose-escalation study of ipilimumab.

    Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1, 8, 15, and 22.
    Treatment with cetuximab repeats every 4 weeks for 2 courses. Beginning in week 2 of course
    1, patients undergo concurrent IMRT 5 days per week for 7 weeks. Beginning in week 4 (day 1
    of course 2) patients also receive ipilimumab IV over 90 minutes once every 21 days for 3
    courses. Treatment continues in the absence of disease progression or unacceptable toxicity.
    Patients achieving disease progression may undergo surgery after completion of therapy.

    After completion of study treatment, patients are followed up every 12 weeks for 1 year,
    every 6 months for 1 year, and then every 12 months for 3 years.

    Trial Arms

    Name Type Description Interventions
    Treatment (cetuximab, IMRT, and ipilimumab) Experimental Patients receive cetuximab IV over 60-120 minutes on days 1, 8, 15, and 22. Treatment with cetuximab repeats every 4 weeks for 2 courses. Beginning in week 2 of course 1, patients undergo concurrent IMRT 5 days per week for 7 weeks. Beginning in week 4 (day 1 of course 2) patients also receive ipilimumab IV over 90 minutes once every 21 days for 3 courses. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may undergo surgery after completion of therapy.

    Eligibility Criteria

    Inclusion Criteria:

    - American Joint Committee on Cancer (AJCC) stage III/IVB, excluding T1N1,
    histologically or cytologically confirmed squamous cell carcinoma or undifferentiated
    carcinoma of the head and neck; patients should not have distant metastasis; primary
    sites include: oropharynx, hypopharynx, larynx

    - Patients must have high or intermediate risk disease, defined as follows:

    - High risk: non-oropharyngeal subsite including larynx or hypopharynx (p16 status
    not required) or human papilloma virus (HPV)/p16- oropharynx subsite

    - Intermediate risk: HPV/p16+ oropharyngeal squamous cell cancer with: >= 10 pack
    (pk)-year (yr) smoking history and >= N2 nodal disease, or the presence of T4
    tumor or N3 nodal disease, irrespective of smoking status

    - Patients must have measurable disease, defined as at least one lesion that can be
    accurately measured in at least one dimension (longest diameter to be recorded for
    non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional
    techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic
    resonance imaging (MRI), or calipers by clinical exam

    - Patients should be newly diagnosed HNSCC, with no prior therapy for this disease

    - Eastern Cooperative Oncology Group (ECOG) performance status typically =< 1
    (Karnofsky >= 70%)

    - Leukocytes >= 3,000/mcL

    - Absolute neutrophil count >= 1,200/mcL

    - Platelets >= 75,000/mcL

    - Total bilirubin =< 2 mg/dL (=< 3 mg/dL in case of Gilbert's syndrome)

    - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2 times
    institutional upper limit of normal (IULN)

    - Creatinine clearance >= 40 mL/min/1.73 m^2

    - Patients must have the ability to understand and to sign written informed consent

    Exclusion Criteria:

    - Patients who have had prior chemotherapy, radiotherapy, or surgery with curative
    intent for HNSCC

    - Patients with a history of prior treatment with ipilimumab, anti-programmed cell
    death 1 (PD 1) antibody, cluster of differentiation 137 (CD137) agonist or other
    immune activating therapy such as anti-cluster of differentiation 40 (CD 40) antibody

    - Patients who are receiving any other investigational agents

    - Autoimmune disease: patients with a history of inflammatory bowel disease, including
    ulcerative colitis and Crohn's disease, are excluded from this study, as are patients
    with a history of symptomatic non-gastrointestinal autoimmune disease (e.g.,
    rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus
    erythematosus, autoimmune vasculitis [e.g., Wegener's granulomatosis]); central
    nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g.
    Guillain-Barre syndrome and myasthenia gravis, multiple sclerosis)

    - Patients with known immunodeficiency disorder, or presumed to be unable to respond to
    anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) monoclonal antibody (mAb)

    - Patients with distant metastatic disease (stage IVC)

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to cetuximab or ipilimumab

    - Patient is < 2 years free from a second primary malignancy unless the other
    malignancy is non-melanomatous skin cancer or an in-situ tumor treated with curative
    intent

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
    arrhythmia, or psychiatric illness/social situations that would limit compliance with
    study requirements; patients with chronic hepatitis B or hepatitis C infections are
    excluded

    - Pregnant women are excluded from this study

    - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
    therapy are ineligible

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Proportion of dose limiting toxicities at each dose level assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Secondary Outcome Measures

    Clinical response by RECIST criteria

    HPV status

    Myeloid-derived suppressor cell (MDSC) cell counts

    Progression free survival

    Serum factors and tumor infiltrates

    T cell phenotypes

    T regulatory cell counts

    Trial Keywords