Radiation Therapy with Cisplatin or Docetaxel and Cetuximab in Treating Patients with Stage III-IVB Head and Neck Cancer
- 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 Response Evaluation Criteria in Solid Tumors (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
- Patients must have measurable disease according to RECIST 1.1
- Absolute neutrophil count (ANC) > 1500/mm^3 (within 4 weeks of registration)
- Hemoglobin (Hb) > 8.0 g/dL (within 4 weeks of registration)
- Platelet count (PLT) > 100,000/mm^3 (within 4 weeks of registration)
- Creatinine clearance >= 45 ml/min determined by 24-hour collection or estimated by the Cockcroft-Gault formula (within 4 weeks of registration)
- Total bilirubin < 2 mg/dL (within 4 weeks of registration)
- AST (aspartate aminotransferase) and ALT (alanine aminotransferase) < 3 times upper limit of normal (ULN) (within 4 weeks of registration)
- The following assessments are required within 14 days prior to registration: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (Mg), and albumin
- The following metabolic laboratory values will exclude patients from study enrollment: * 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; 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 * 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
- 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; pregnant women are excluded from this study
- 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
- Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study; 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
I. To evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab versus (vs.) cisplatin in patients with previously untreated locally advanced (PULA) head and neck squamous cell carcinoma (HNSCC) and increased tumoral excision repair cross-complementing group 1 (ERCC1) expression, as measured by time to progression (TTP).
I. To 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 time to progression (TTP).
II. To evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab vs. cisplatin, as measured by locoregional control (LRC) and rates of distant metastases, in: 1) patients with PULA HNSCC and increased tumoral ERCC1 expression; 2) patients with PULA HNSCC and decreased/normal ERCC1 expression; 3) all patients irrespective of ERCC1 status.
III. To externally and prospectively validate the candidate cutpoint for decreased/normal vs. increased ERCC1 expression.
IV. To compare treatment effects (docetaxel-cetuximab vs cisplatin) between decreased/normal and high ERCC1 groups.
V. To explore biomarker by treatment interactions for alternative biomarkers.
VI. To evaluate patient-related perceptions of quality of life (QOL), cognitive function and pain in patients with PULA HNSCC treated with radiotherapy concurrent with docetaxel-cetuximab vs. cisplatin.
VII. To develop alternate scoring methodologies for ERCC1 expression, and evaluate the relationship to clinical outcomes following radiotherapy with concurrent docetaxel-cetuximab vs. cisplatin.
VIII. To investigate whether specific molecular or immune profiles are associated with clinical outcomes.
IX. To prospectively investigate two sets of radiologic interpretive criteria for the designation of complete response (CR), to evaluate the agreement of these interpretive criteria for designation of CR, and to compare the ability of the two CR classifications to accurately predict superior TTP.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM A: Patients receive cisplatin intravenously (IV) over 1-2 hours once weekly for 7 weeks and undergo intensity modulated radiation therapy (IMRT) once daily (QD) five days a week for 7 weeks.
ARM B: Patients receive cetuximab IV over 120 minutes 4-8 days prior to the first radiation treatment. Patients then receive cetuximab IV over 60 minutes and docetaxel IV once weekly and undergo IMRT QD five days a week for 7 weeks.
After completion of study treatment, patients are followed up at 6 weeks, every 3 months for 2 years, then every 6 months for 3 years.
Trial Phase Phase II
Trial Type Treatment
University of Pittsburgh Cancer Institute (UPCI)
Julie E. Bauman
- Primary ID UPCI 13-056
- Secondary IDs NCI-2014-01116, PRO13080400, 13-056
- Clinicaltrials.gov ID NCT02128906