Erlotinib Hydrochloride and Radiation Therapy in Stage III-IV Squamous Cell Cancer of the Head and Neck

Phase 2

Terminated

Conditions: 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 Oropharynx
Stage IV Verrucous Carcinoma of the Oral Cavity
Stage III Squamous Cell Carcinoma of the Hypopharynx
Stage III Squamous Cell Carcinoma of the Larynx
Stage III Verrucous Carcinoma of the Larynx
Stage IV Squamous Cell Carcinoma of the Nasopharynx
Stage IV Verrucous Carcinoma of the Larynx
Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity

Interventions: Drug: erlotinib hydrochloride
Radiation: intensity-modulated radiation therapy
Other: pharmacogenomic studies
Other: gene expression analysis
Radiation: 3-dimensional conformal radiation therapy
Other: biopsy
Other: pharmacological study
Other: laboratory biomarker analysis
Other: questionnaire administration
Other: enzyme-linked immunosorbent assay
Other: polymorphism analysis

Registration Number: NCT01192815

Lead Sponsor: Case Comprehensive Cancer Center

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2

Inclusion Criteria

Patients must have histologically or cytologically confirmed locally advanced (stage III or IV) squamous cell carcinoma of the head and neck without distant metastatic disease, who are not candidates or have declined definitive surgical resection or for administration of standard chemotherapy during radiation therapy because of any of the following reasons: advanced age (>= 70 years); poor ECOG performance status (2 or 3); significant comorbidities, as reflected by a Charlson comorbidity index score of >= 3; abnormal hematopoietic, hepatic or renal function; patient's decision after applicable standard treatment options have been offered and declined by patient
No prior chemotherapy, radiation therapy, or investigational antitumor drug
Measurable disease within 4 weeks prior to registration according to the recommended RECIST response criteria
Life expectancy of greater than 12 weeks
Patients must have normal hepatic function or well compensated liver disease as defined by the Child-Pugh classification of severity of liver disease; patients with hepatic impairment (total bilirubin greater than upper limit of normal [ULN] or well-compensated disease [Child-Pugh class A] enrolled in the trial will be closely monitored, especially those with total bilirubin > 3 times ULN; dosage modifications (therapy interruption or discontinuation) may be necessary for severe changes in liver function; patient management will follow the FDA-approved labeling recommendations
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
Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter
Women of childbearing potential must have a negative pregnancy test; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

All histologies other than squamous cell carcinoma
Salivary gland paranasal sinus and nasopharyngeal squamous cell carcinoma
Patients who have had prior chemotherapy or radiotherapy
Patients with metastatic disease
Patients with ECOG performance status of 4
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ERLOTINIB
Patients with history of any other malignancy (except squamous cell or basal cell cancer of the skin or CIS of cervix) are ineligible unless a period of 5 years has elapsed since treatment of the previous cancer and the patient is currently disease-free from the previous cancer
Patients may not be receiving any other investigational agent
Pregnant women; breastfeeding should be discontinued

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	erlotinib hydrochloride	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.
Arm I	intensity-modulated radiation therapy	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.
Arm I	pharmacogenomic studies	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.
Arm I	gene expression analysis	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.
Arm I	3-dimensional conformal radiation therapy	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.
Arm I	biopsy	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.
Arm I	pharmacological study	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.
Arm I	laboratory biomarker analysis	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.
Arm I	questionnaire administration	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.
Arm I	enzyme-linked immunosorbent assay	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.
Arm I	polymorphism analysis	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.

Primary Outcome Measures

Name	Time	Method
Time to Disease Progression	1 year and 10 months following study start	The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or PD is objectively documented, taking as reference for PD the smallest measurements recorded since the treatment started. Disease progression free survival (PFS) is measured from start of treatment to the date of disease progression or protocol-designated outcome, whichever occurs first and censored at the date of last followed for those survivors without disease progression Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Measured via Conventional CT and MRI

Secondary Outcome Measures

Name	Time	Method
Toxicities, Number of Persons With Adverse Events	up to 2 yrs after treatment	Number of participants who experienced adverse events (AE's) and serious adverse events (SAE's) during the course of the trial according to CTCAE (4.0)
Locoregional Control Rate	5 yrs following treatment
Quality of Life Assessment as Measured by Functional Assessment of Cancer Therapy (FACT-G) Test	after treatment at 6 mos	Quality of Life (QOL) measured using the Functional Assessment of Cancer Therapy-General (FACT-G) on a 0-108 scale, with lower scores corresponding to worse overall QOL and higher scores corresponding to better overall QOL.
Objective Response Rate	1 year and 10 months following study start	Number of patients with complete response, partial response, stable disease, or progressive disease. Assessed via Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Measured via conventional CT and MRI
Patterns of Failure	5 yrs following treatment

Trial Locations

Locations (1): Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
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Cleveland, Ohio, United States