Radiation Therapy With Cisplatin or Docetaxel and Cetuximab in Treating Patients With Stage III-IVB Head and Neck Cancer
Basic Trial Information
|Phase II||Biomarker/Laboratory analysis, Treatment||Active||18 and over||UPCI 13-056|
NCI-2014-01116, 13-056, PRO13080400, NCT02128906
This randomized phase II trial studies how well radiation therapy in combination with cisplatin or docetaxel and cetuximab works in treating patients with stage III-IVB head and neck cancer. Radiation therapy uses high energy x rays to kill tumor cells. Docetaxel is designed to stop the growth of cancer cells, which may cause the cells to die. It may also damage blood vessels in tumor tissue. Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the epidermal growth factor receptor (EGFR). Cisplatin has a platinum atom at its center. The platinum may poison the cancer cells, which may cause them to die. It is not yet known whether radiation therapy is more effective when given with cisplatin or docetaxel and cetuximab in treating patients with head and neck cancer.
Further Study Information
I. To evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab 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, every 6 months for 2 years, and yearly for 1 year.
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
Hemoglobin (Hb) > 8.0 g/dL
Platelet count (PLT) > 100,000/mm^3
Creatinine clearance >= 45 ml/min determined by 24-hour collection or estimated by the Cockroft-Gault formula
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: sodium (Na), potassium (K), chloride (Cl), glucose, calcium (Ca), magnesium (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; 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
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
University of Pittsburgh Cancer Institute (UPCI)
- National Cancer Institute
University of Pittsburgh Cancer Institute (UPCI)
Julie E. Bauman
Julie E. Bauman
University of Washington Medical Center
Renato Goncalves Martins
Renato Goncalves Martins
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT02128906
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.