Erlotinib, Docetaxel, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer - Full Text View

Sponsor:	Case Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00049283

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining erlotinib with docetaxel may make the tumor cells more sensitive to radiation therapy and may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combining erlotinib with docetaxel and radiation therapy in treating patients who have locally advanced head and neck cancer.

Condition	Intervention	Phase
Head and Neck Cancer	Drug: docetaxel Drug: erlotinib hydrochloride Procedure: conventional surgery Radiation: radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, OSI-774, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck

Resource links provided by NLM:

MedlinePlus related topics: Cancer Head and Neck Cancer

Drug Information available for: Docetaxel Erlotinib hydrochloride Erlotinib

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Toxicity as measured by physical exams every 2 weeks during treatment, and blood tests weekly [ Time Frame: every 2 weeks during treatment, and blood tests weekly ] [ Designated as safety issue: Yes ]
Disease response measured 6-8 weeks after completion of study treatment [ Time Frame: measured 6-8 weeks after completion of study treatment ] [ Designated as safety issue: No ]
Maximum tolerated dose as measured by CTC v3.0 at end of phase I study [ Time Frame: measured by CTC v3.0 at end of phase I study ] [ Designated as safety issue: Yes ]

Enrollment:	24
Study Start Date:	September 2002
Primary Completion Date:	March 2006 (Final data collection date for primary outcome measure)

Intervention Details:

Docetaxel IV over 1 hour on day 3 of weeks 3-9.

Oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral erlotinib daily beginning on day 1. Patients continue erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity.

Neck dissection 6-8 weeks after completion of chemoradiotherapy.

Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9.

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of erlotinib when administered with docetaxel and radiotherapy in patients with locally advanced squamous cell cancer of the head and neck.
Determine the toxicity of this regimen in these patients.
Determine the pharmacokinetic profile of erlotinib alone and in combination with docetaxel in these patients.
Determine the overall and complete response rate in patients treated with this regimen.
Determine the overall, disease-free, and progression-free survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of erlotinib and docetaxel.

Patients receive oral erlotinib alone daily on weeks 1 and 2. Patients then receive oral erlotinib daily beginning on day 1 and docetaxel IV over 1 hour on day 3 of weeks 3-9. Patients also undergo radiotherapy once daily 5 days a week on weeks 3-9. Patients continue erlotinib for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients who had N2 or greater cervical lymph node involvement at baseline or have residual neck adenopathy after chemoradiotherapy undergo neck dissection 6-8 weeks after completion of chemoradiotherapy. Erlotinib is held for 1 week before planned surgery and until healing is complete.

Cohorts of 3-6 patients receive escalating doses of erlotinib and docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 16 weeks for 1 year after completion of erlotinib, every 24 weeks for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed squamous cell carcinoma of the head and neck
- Stage III or IV (locally advanced disease)
- No distant metastatic disease
Measurable disease
No salivary gland or 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:

Age

18 and over

Performance status

ECOG 0-2 OR
Karnofsky 60-100%

Life expectancy

More than 12 weeks

Hematopoietic

Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin at least 10 g/dL

Hepatic

Bilirubin normal
AST/ALT no greater than 2 times upper limit of normal
Prothrombin time normal

Renal

Creatinine normal OR
Creatinine clearance at least 60 mL/min

Cardiovascular

No clinically significant heart disease
No New York Heart Association class III or IV heart disease
No significant arrhythmias requiring medication
No symptomatic coronary artery disease
No myocardial infarction within the past 6 months
No second- or third-degree heart block or bundle branch block
No symptomatic congestive heart failure
No unstable angina pectoris

Other

No prior allergic reactions attributed to compounds of similar chemical or biological composition to erlotinib or docetaxel, including other drugs formulated with polysorbate 80
No pre-existing peripheral neuropathy grade 2 or greater
No other concurrent uncontrolled illness that would preclude study participation
No ongoing or active infection
No psychiatric illness or social situation that would preclude study participation
No other malignancy within the past 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
No patients who are considered poorly compliant
HIV negative
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent routine colony-stimulating factors

Chemotherapy

No prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

No prior radiotherapy

Surgery

Not specified

Other

No prior investigational antitumor drugs
No other concurrent commercial or investigational anticancer agents or therapies

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049283

Locations

United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Panos Savvides, MD

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center ( Panos Savvides, MD )
Study ID Numbers:	CWRU1301, U01CA062502, P30CA043703, CASE-CWRU-1301, NCI-5389, CWRU-050212, CASE-1301
Study First Received:	November 12, 2002
Last Updated:	February 25, 2010
ClinicalTrials.gov Identifier:	NCT00049283 History of Changes
Health Authority:	United States: Federal Government; United States: Food and Drug Administration

Keywords provided by Case Comprehensive Cancer Center:

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 nasopharynx
stage III squamous cell carcinoma of the oropharynx

stage IV squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the larynx
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

Additional relevant MeSH terms:

Erlotinib
Docetaxel
Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Head and Neck Neoplasms
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on March 18, 2010