Clinical Trials /

Radiotherapy With Cisplatin vs. Docetaxel-cetuximab in HNSCC: ERCC1 Biomarker Enrichment and Interaction Design

NCT02128906

Description:

The goal of this clinical research study is to learn which chemotherapy combination may be more effective in treating locally advanced head and neck squamous cell carcinoma (HNSCC). The side effects of these combinations will also be studied. This study treatment consists of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy. For study chemotherapy, patients will be randomized between cisplatin or the combination of docetaxel and cetuximab. Subjects will be stratified depending on HPV status and the presence of ERCC-1 [4F9] in the tumor prior to randomization. The study will evaluate cisplatin vs. docetaxel-cetuximab in the overall population, and test which radiation and chemotherapy combination works best in relationship to how much ERCC-1 [4F9] is expressed in a tumor.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Radiotherapy</span> With <span class="go-doc-concept go-doc-intervention">Cisplatin</span> vs. <span class="go-doc-concept go-doc-intervention">Docetaxel</span>-<span class="go-doc-concept go-doc-intervention">cetuximab</span> in HNSCC: <span class="go-doc-concept go-doc-biomarker">ERCC1</span> Biomarker Enrichment and Interaction Design

Title

  • Brief Title: Radiotherapy With Cisplatin vs. Docetaxel-cetuximab in HNSCC: ERCC1 Biomarker Enrichment and Interaction Design
  • Official Title: A Randomized, Phase II Study of Definitive Radiotherapy With Concurrent Cisplatin vs. Docetaxel-cetuximab in Locally Advanced Head and Neck Squamous Cell Carcinoma: an ERCC1 Biomarker Enrichment and Interaction Design
  • Clinical Trial IDs

    NCT ID: NCT02128906

    ORG ID: UPCI 13-056

    Trial Conditions

    Squamous Cell Carcinoma of the Oropharynx, Larynx, or Hypopharynx

    Trial Interventions

    Drug Synonyms Arms
    Cisplatin Cisplatin-IMRT
    Docetaxel Docetaxel-Cetuximab-IMRT
    Cetuximab Docetaxel-Cetuximab-IMRT

    Trial Purpose

    The goal of this clinical research study is to learn which chemotherapy combination may be
    more effective in treating locally advanced head and neck squamous cell carcinoma (HNSCC).
    The side effects of these combinations will also be studied.

    This study treatment consists of intensity-modulated radiation therapy (IMRT) and concurrent
    chemotherapy. For study chemotherapy, patients will be randomized between cisplatin or the
    combination of docetaxel and cetuximab. Subjects will be stratified depending on HPV status
    and the presence of ERCC-1 [4F9] in the tumor prior to randomization. The study will
    evaluate cisplatin vs. docetaxel-cetuximab in the overall population, and test which
    radiation and chemotherapy combination works best in relationship to how much ERCC-1 [4F9]
    is expressed in a tumor.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Cisplatin-IMRT Active Comparator Cisplatin 40 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy) Cisplatin
    Docetaxel-Cetuximab-IMRT Active Comparator Docetaxel 15 mg/m2 weekly x 7; Cetuximab 400 mg/m2 load, one week prior to IMRT; Cetuximab 250 mg/m2 weekly x 7; IMRT: once daily, M-F, 7 weeks (70 Gy) Docetaxel, Cetuximab

    Eligibility Criteria

    Inclusion Criteria:

    - Pathologically confirmed squamous cell carcinoma, undifferentiated carcinoma, or
    poorly differentiated carcinoma of the oropharynx, larynx, or hypopharynx with no
    evidence of distant metastasis. Biopsy sampling of primary tumor with pathology
    report documenting diagnostic tissue type is required.

    - Patients must have stage III, IVa or IVb disease as determined by imaging studies and
    complete head and neck exam. Staging evaluation should be in accordance with the
    American Joint Committee on Cancer Staging Manual, 7th edition.

    - Patients with oropharyngeal squamous cell carcinoma may have p16(+) or p16(-)
    disease; in these patients, p16 status must be known prior to randomization.
    Assessment of p16 status may occur locally or centrally. Note: The definition of
    p16(+) disease is diffuse nuclear and cytoplasmic staining in 70% of tumor cells.

    - Patients must be untreated with curative-intent surgery for current diagnosis of
    Stage III, IVa, or IVb disease. Diagnostic biopsy of primary tumor and/or nodal sites
    is permitted.

    - Diagnostic simple tonsillectomy is permitted, provided patient has RECIST-measurable
    residual tumor and/or nodal disease.

    - Patients with a second HNSCC primary tumor are eligible for this study, provided more
    than 2 years have elapsed since the first diagnosis of HNSCC, the original tumor was
    managed with surgery only (no adjuvant chemotherapy/radiotherapy), and has not
    recurred.

    - Patients with simultaneous primaries or bilateral tumors are excluded, with the
    exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0
    resected differentiated thyroid carcinoma, who are eligible.

    - No prior systemic treatment (chemotherapy or biologic/molecular targeted therapy) or
    radiation treatment for head and neck cancer.

    - Patients may have received chemotherapy or radiation for a previous, curatively
    treated non-HNSCC malignancy, provided at least 2 years have elapsed.

    - Patients must be untreated with radiation above the clavicles.

    - Patients with a history of curatively-treated non-HNSCC malignancy must be
    disease-free for at least 2 years except for carcinoma-in-situ of cervix,
    non-melanomatous skin cancer, or T1-2, N0, M0 resected differentiated thyroid
    carcinoma.

    - Diagnostic primary tumor tissue must be available for ERCC1 staining

    - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (See Appendix 8)

    - Age 18

    - Patients must have measurable disease according to RECIST 1.1

    - Patients must have the following laboratory values measured within 14 days of
    registration:

    - Absolute neutrophil count (ANC) > 1500/mm3

    - Hemoglobin (Hb) > 8.0 g/dL

    - Platelet count (PLT) > 100,000/mm3

    - Creatinine clearance 45 ml/min determined by 24-hour collection or estimated by the
    Cockraft-Gault formula:

    Calculated Creatinine Clearance = [(140-age) X (actual body weight in kg) X (0.85 if
    female)]/(72 X serum creatinine)

    - Serum bilirubin < 2 mg/dL

    - AST (aspartate aminotransferase) and ALT (alanine aminotransferase) < 3 times upper
    limit of normal (ULN)

    - The following assessments are required within 14 days prior to registration: Na, K,
    Cl, glucose, Ca, Mg, and albumin. The following metabolic values will exclude
    patients from study enrollment:

    - Serum calcium (ionized or adjusted for albumin) < 7 mg/dl (1.75 mmol/L) or > 12.5
    mg/dl (> 3.1 mmol/L) despite intervention to normalize levels

    - Magnesium < 0.9 mg/dl (< 0.4 mmol/L) or > 3 mg/dl (> 1.23 mmol/L) despite
    intervention to normalize levels

    - Potassium < 3.5 mmol/L or > 6 mmol/L despite intervention to normalize levels

    - Sodium < 130 mmol/L or > 155 mmol/L despite intervention to normalize levels Note:
    Patients with an initial magnesium < 0.5 mmol/L (1.2 mg/dl) may receive corrective
    magnesium supplementation but should continue to receive either prophylactic weekly
    infusion of magnesium and/or oral magnesium supplementation (eg, magnesium oxide) at
    the investigator's discretion.

    - No prior severe infusion reaction to a monoclonal antibody

    - Written informed consent must be obtained from all patients prior to beginning
    therapy. Patients should have the ability to understand and the willingness to sign a
    written informed consent document.

    - Informed consent must be obtained from all patients prior to beginning therapy,
    including consent for mandatory tissue submission for ERCC1 staining (and p16
    staining if not locally conducted). Patients should have the ability to understand
    and the willingness to sign a written informed consent document.

    - No unstable angina or myocardial infarction within the prior 6 months; no symptomatic
    congestive heart failure; no serious cardiac arrhythmia requiring medication; no
    cerebrovascular ischemia or stroke within the past 6 months.

    - No uncontrolled intercurrent illness including active infection, uncontrolled
    diabetes, uncontrolled hypertension, or uncontrolled psychiatric illness which in the
    investigator's opinion would limit compliance with study requirements or compromise
    patient safety.

    - Women must not be pregnant or breast feeding because chemotherapy and/or cetuximab
    may be harmful to the fetus or the nursing infant. Pregnant women are excluded from
    this study because chemotherapy and/or cetuximab have the potential for teratogenic
    or abortifacient effects.

    - Women of child-bearing potential and men must agree to use adequate contraception
    (hormonal or barrier method of birth control) prior to study entry and for the
    duration of study participation. Should a woman become pregnant or suspect she is
    pregnant while in this study, she should inform her treating physician immediately.
    All females of childbearing potential must have a blood test or urine study within 14
    days of registration to rule out pregnancy.

    - HIV-positive patients receiving combination anti-retroviral therapy are excluded from
    the study because of possible drug interactions with study drugs. Appropriate studies
    will be undertaken in patients receiving combination anti-retroviral therapy when
    indicated. Note: HIV testing is not required for entry into this protocol.

    - Patients may not be receiving any other anti-neoplastic investigational agents.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab vs. cisplatin in patients with locally advanced HNSCC and increased tumoral ERCC1 expression, as measured by time to progression (TTP)

    Secondary Outcome Measures

    Evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab vs. cisplatin in patients with PULA HNSCC and decreased/normal tumoral ERCC1 expression, as measured by TTP

    Evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab vs. cisplatin in all patients irrespective of ERCC1 status, as measured by TTP

    Prospectively validate the candidate cutpoint for decreased/normal vs. increased ERCC1 [4F9] expression in patients treated with cisplatin-IMRT

    Prospectively investigate two sets of radiologic interpretive criteria, including RECIST 1.1 and integrated PET/CT, for the designation of complete response (CR), and to compare the ability of the two CR classifications to accurately predict 2-year TTP.

    Trial Keywords

    ERCC1

    squamous cell carcinoma

    oropharynx

    larynx

    hypopharynx

    p16

    radiotherapy

    docetaxel

    cetuximab

    cisplatin

    EGFR

    Biomarker

    efficacy