Clinical trial NCT00720304: Erlotinib, Docetaxel, and Radiation Therapy in Stage III or Stage IV Squamous Cell Carcinoma of the Head and Neck
Official title: A Phase II Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Erlotinib, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: stage III squamous cell carcinoma of the hypopharynx
stage IV 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 larynx
stage IV verrucous carcinoma of the larynx
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage III verrucous carcinoma of the oral cavity
stage IV verrucous carcinoma of the oral cavity
metastatic squamous neck cancer with occult primary squamous cell carcinoma
stage III squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2008-07-22
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percent of Participants With Disease-Free Survival (DFS) at 3 Years
timeFrame: 3 yrs after treatment
measure: Time to Progression (TTP)
timeFrame: 3 yrs after treatment
Secondary outcomes:
measure: Response Rate (Complete Response, Partial Response, Stable Disease, and Disease Progression)
timeFrame: 3 yrs after treatment
measure: Overall Survival (OS)
timeFrame: 3 years
measure: Number of Participants With Acute Grade III/IV Treatment-related Toxicities
timeFrame: evaluated every 2 weeks, up to 3 years
measure: Percent of Participants With Local Failure-free Survival
timeFrame: At 3 years
measure: Percent of Participants With Regional Failure-free Survival
timeFrame: At 3 years
measure: Percent of Participants With Locoregional Failure-free Survival
timeFrame: At 3 years
measure: Percent of Participants With Distant Metastasis-free Survival
timeFrame: At 3 years
Other outcomes:
measure: Predictive Values of EGFR/TGF-α, VEGF
timeFrame: collection at baseline and periodically during study.
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
name: Min Yao, MD
role: PRINCIPAL_INVESTIGATOR
References: