Clinical trial NCT01192815
Conditions: Stage III Squamous Cell Carcinoma of the Hypopharynx Stage III Squamous Cell Carcinoma of the Larynx Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity Stage III Squamous Cell Carcinoma of the Oropharynx Stage III Verrucous Carcinoma of the Larynx Stage III Verrucous Carcinoma of the Oral Cavity Stage IV Squamous Cell Carcinoma of the Hypopharynx Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity Stage IV Squamous Cell Carcinoma of the Nasopharynx Stage IV Squamous Cell Carcinoma of the Oropharynx Stage IV Verrucous Carcinoma of the Larynx Stage IV Verrucous Carcinoma of the Oral Cavity
Sponsor: Case Comprehensive Cancer Center
Start date: 2011-01-01; Completion date: 2012-10-01
Enrollment: 2 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Erlotinib hydrochloride may also make tumor cells more sensitive to radiation therapy. Radiation therapy uses high-energy x- rays and other types of radiation to kill tumor cells. Giving erlotinib hydrochloride together with radiation therapy may be an effective treatment for patients with head and neck cancer.PURPOSE: This phase II trial is studying how well giving erlotinib hydrochloride together with radiation therapy works in treating patients with stage III-IV squamous cell cancer of the head and neck.

Detailed description:
PRIMARY OBJECTIVES:I. To determine the time to progression of the combination of the EGFR inhibitor erlotinib and radiation therapy. SECONDARY OBJECTIVES:I. To determine objective response rate, locoregional control rate, duration of response, patterns of failure, overall survival, toxicities and quality of life outcomes of the combination of erlotinib and concurrent radiation therapy.II. To determine the pharmacokinetic profile of erlotinib. Additional analyses of the pharmacokinetic data on patients receiving daily erlotinib treatment via their feeding tube will be conducted. III. To determine the effect of treatment and dose of treatment on biologic correlates in tumor tissue and/or surrounding mucosa, EGFR expression and phosphorylation status, serum markers of angiogenic activity VEGF, sVEGFR-2, sKIT, ICAM, PDGF, fluorescence in situ hybridization (FISH) for ERBB2 for gene amplification, DNA-sequencing of EGFR and ERBB2 genes from DNA extracted from pretreatment biopsy material for mutation screening, gene expression profiling on pre-treatment biopsy material to identify predictors of response to treatment, apoptosis (TUNEL assay), Ki67 (nuclear proliferation antigen)IV. To determine the utility of the comprehensive geriatric assessment, in predicting tolerance to treatment in patients \>= 65 years included in this trial. OUTLINE: Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.After completion of study treatment, patients are followed up at 6 months, every 3 months for 2 years, and then every 6 months for 2 years.

Arms: arm 1: Patients receive erlotinib hydrochloride orally or via gastrostomy tube once daily in weeks 1-9 and then for 2 years following completion of radiation therapy. Beginning on day 1 of week 2, patients undergo radiation therapy once daily, 5 times a week, for 5-7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: erlotinib hydrochloride intervention 2: intensity-modulated radiation therapy intervention 3: pharmacogenomic studies intervention 4: gene expression analysis intervention 5: 3-dimensional conformal radiation therapy intervention 6: biopsy intervention 7: pharmacological study intervention 8: laboratory biomarker analysis intervention 9: questionnaire administration intervention 10: enzyme-linked immunosorbent assay intervention 11: polymorphism analysis
Intervention descriptions: intervention 1: Given orally or via gastronomy tube intervention 2: IMRT will be given in 35 fractions over 7 weeks. The primary tumor and involved nodes (PTV70) will receive 2 Gy per fractions, intermediate-risk areas (PTV63) will receive 1.8 Gy per fractions, and subclinical disease sites (PTV56) will receive 1.6 Gy perfraction. The total doses will thus be 70 Gy, 63 Gy and 56 Gy, respectively. intervention 3: Optional correlative studies intervention 4: Correlative studies intervention 5: The initial target volume encompassing the gross and subclinical disease sites will receive 2.0 Gy per fraction, five fractions a week to 54 Gy in 27 fractions in 5.4 weeks. The boost volume covering gross tumor and clinically/radiologically involved nodes will receive boost irradiation for additional 16 Gy at 2.0 Gy. The primary tumor and clinically/radiologically-involved nodes will thus receive 70 Gy in 35 fractions over 7 weeks, and uninvolved upper neck nodes will receive an elective dose of 54 Gy in 5.4 weeks.

The uninvolved lower neck nodes will receive 2.0 Gy per fraction at 3-cm depth to a total dose of 50 Gy in 25 fractions in 5.0 weeks through a matching AP or AP/PA lower neck field. intervention 6: Optional correlative studies intervention 7: Optional correlative studies intervention 8: Optional correlative studies intervention 9: Optional ancillary studies intervention 10: Optional correlative studies intervention 11: Optional correlative studies

Protocol documents: