Erlotinib, Docetaxel, and Radiation Therapy in Stage III or Stage IV Squamous Cell Carcinoma of the Head and Neck

Phase 2CompletedNCT00720304

Case Comprehensive Cancer Center43 enrolled

Overview

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with docetaxel and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well erlotinib given together with docetaxel and radiation therapy works in treating patients with stage III or stage IV squamous cell carcinoma of the head and neck.

OBJECTIVES: Primary * Determine the time to progression in patients with locally advanced squamous cell carcinoma of the head and neck treated with erlotinib hydrochloride in combination with docetaxel and radiotherapy. Secondary * Determine objective response rate, locoregional control rate, duration of response, patterns of failure, and overall survival in patients treated with this regimen. * Determine the toxicities of this regimen in these patients. * Determine the dose and effect of this treatment on biologic correlates in tumor tissue and/or surrounding mucosa. OUTLINE: This is a multicenter study. Patients receive oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Beginning on week 3, patients receive docetaxel IV over 1 hour once a week and radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity. At 6-8 weeks after completion of chemoradiotherapy, patients with N2 or greater cervical lymph node involvement at baseline or with residual disease may undergo surgery. Patients with persistent disease during study therapy undergo salvage surgery 6-12 weeks after completion of chemoradiotherapy. Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR. After completion of study therapy, patients will be evaluated every 4-8 weeks for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then once a year thereafter.

Study Type

INTERVENTIONAL

Interventions

docetaxelDRUG

Beginning on week 3, patients receive docetaxel IV over 1 hour once a week

erlotinib hydrochlorideDRUG

oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity

fluorescence in situ hybridizationGENETIC

Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.

polymerase chain reactionGENETIC

immunoenzyme techniqueOTHER

immunohistochemistry staining methodOTHER

laboratory biomarker analysisOTHER

pharmacological studyOTHER

therapeutic conventional surgeryPROCEDURE

At 6-8 weeks after completion of chemoradiotherapy, patients with N2 or greater cervical lymph node involvement at baseline or with residual disease may undergo surgery.Patients with persistent disease during study therapy undergo salvage surgery 6-12 weeks after completion of chemoradiotherapy.

intensity-modulated radiation therapyRADIATION

radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.

radiation therapyRADIATION

radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed locally advanced squamous cell carcinoma of the head and neck * Stage III or IV disease * No distant metastatic disease * Measurable disease (according to RECIST) * No salivary gland and paranasal sinus squamous cell carcinoma * No known brain metastases or direct cerebral invasion by tumor * Intracranial extension (without cerebral involvement) may be allowed PATIENT CHARACTERISTICS: * ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% * Life expectancy \> 12 weeks * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥10 g/dL * Total bilirubin normal * Alkaline phosphatase AND AST and ALT meeting the following criteria: * Alkaline phosphatase normal AND AST and ALT ≤ 5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN AND AST and ALT ≤ 2.5 times ULN * Alkaline phosphatase ≤ 5 times ULN AND AST and ALT normal * Creatinine normal OR creatinine clearance ≥ 60 mL/min * No clinically significant heart disease including any of the following: * NYHA class III or IV heart disease * Significant arrhythmias requiring medication * Symptomatic coronary artery disease * Myocardial infarction within the previous six months * Second- or third-degree heart block or bundle-branch block * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or docetaxel, including other drugs formulated with polysorbate 80 * No pre-existing peripheral neuropathy ≥ grade 2 * No uncontrolled concurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would preclude compliance with study requirements * No HIV positivity * No other prior malignancy except for any of the following: * Squamous cell or basal cell carcinoma of the skin * Carcinoma in situ of the cervix * Cancer that was treated more than 5 years ago and the patient has remained disease-free * Not poorly compliant PRIOR CONCURRENT THERAPY: * No prior chemotherapy, radiotherapy, or investigational antitumor drug * No other concurrent investigational agents

Outcomes

Primary Outcomes

Percent of Participants With Disease-Free Survival (DFS) at 3 Years

Percent of participants with Disease-Free survival (DFS) at 3 years. Assessed from date of treatment to date of death or date of disease progression, and to date of last follow-up for those still alive and progression free. Disease-free Survival percentages were calculated using Kaplan-Meier estimates.

Time frame: 3 yrs after treatment

Time to Progression (TTP)

Time from start of treatment to first documented occurrence of progressive disease (PD). PD defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Time frame: 3 yrs after treatment

Secondary Outcomes

Response Rate (Complete Response, Partial Response, Stable Disease, and Disease Progression)

Response rate according to response criteria, which defines the following: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions

Time frame: 3 yrs after treatment

Overall Survival (OS)

Percent of participants alive at follow-up time. Overall survival time is evaluated from the date of treatment to date of death, and to date of last follow-up for those still alive.

Time frame: 3 years

Number of Participants With Acute Grade III/IV Treatment-related Toxicities

Number of participants with acute grade III/IV treatment-related toxicities

Time frame: evaluated every 2 weeks, up to 3 years

Percent of Participants With Local Failure-free Survival

Participants with Local absence of relapse or recurrence or progression within the prescribed radiation field.

Time frame: At 3 years

Percent of Participants With Regional Failure-free Survival

Participants with the regional absence of relapse or recurrence or progression within the prescribed radiation field. Failure-free Survival percentages were calculated using Kaplan-Meier estimates.

Time frame: At 3 years

Percent of Participants With Locoregional Failure-free Survival

Participants with the locoregional absence of relapse or recurrence or progression within the prescribed radiation field. Locoregional failure-free survival percentages were calculated using Kaplan-Meier estimates.

Time frame: At 3 years

Percent of Participants With Distant Metastasis-free Survival

Percent of participants with distant metastasis-free survival

Time frame: At 3 years

Erlotinib, Docetaxel, and Radiation Therapy in Stage III or Stage IV Squamous Cell Carcinoma of the Head and Neck

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes