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.
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.
None
Parallel
Cisplatin
DrugCisplatin 40 mg/m2 weekly x 7
IMRT
RadiationIMRT: once daily, M-F, 7 weeks (70 Gy)
Docetaxel
DrugDocetaxel 15 mg/m2 weekly x 7
Cetuximab
DrugCetuximab 400 mg/m2 load, one week prior to IMRT Cetuximab 250 mg/m2 weekly x 7
Time To Progression (TTP)
Time To Progression is the duration of time from date of study entry until the first appearance of new metastatic lesions or objective tumor progression in patients with increased tumoral ERCC1 expression. Progression is defined per RECIST v1.1 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time to progression (TTP)
Time To Progression is the duration of time from date of study entry until the appearance of new metastatic lesions or objective tumor progression in patients with decreased tumoral ERCC1 expression. Progression is defined per RECIST v1.1 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Local Control Rate (LRC)
Proportions of patients with a tumor volume equal to or less than the tumor volume at start of radiotherapy.
Rate of distant metastases
Proportion of patients with new metastatic lesions or objective tumor progression in patients with increased tumoral ERCC1 expression. Progression is defined per RECIST v1.1 as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Validation candidate cutpoint
Validation candidate cutpoint for decreased/normal vs. increased ERCC1 \[4F9\] expression in patients treated with cisplatin-IMRT. ERCC1 \[4F9\] expression is measured.
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Christopher Wilke
Lead sponsor
University of Pittsburgh
Sponsor institution
