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Adjuvant Erlotinib After Completing Chemoradiotherapy in Treating Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
This study is ongoing, but not recruiting participants.
Sponsored by: National Cancer Institute of Canada
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00079053
  Purpose

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving erlotinib after chemoradiotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of adjuvant erlotinib when given after completing chemoradiotherapy in treating patients with locally advanced squamous cell carcinoma (cancer) of the head and neck.


Condition Intervention Phase
Head and Neck Cancer
Drug: erlotinib hydrochloride
Procedure: adjuvant therapy
Phase I

MedlinePlus related topics: Cancer Head and Neck Cancer Salivary Gland Disorders
Drug Information available for: Erlotinib Erlotinib hydrochloride
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase I Study of Adjuvant OSI-774 (Tarceva®) in Patients Following Combined Chemo-Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Toxicity/feasibility assessed by NCI CTC v2.0 at the end of course 1 [ Designated as safety issue: Yes ]
  • Recommended phase II dose at the end of course 1 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Correlative studies (archival and prospective) at accrual completion [ Designated as safety issue: No ]
  • Disease-free survival [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: November 2003
Estimated Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the recommended dose of adjuvant erlotinib after the completion of chemoradiotherapy in patients with stage III, IVA, or IVB squamous cell carcinoma of the head and neck.
  • Determine the toxicity of this drug in these patients.
  • Determine the effects of this drug on plasma and urinary angiogenic factors (specifically vascular endothelial growth factor receptor [VEGFR], VEGFR1, VEGFR2, and basic fibroblast growth factor levels) in these patients.
  • Compare the disease-free survival of patients treated with this drug after chemoradiotherapy vs historical control patients treated with chemoradiotherapy alone.
  • Correlate levels of angiogenic factors with initial blood vessel concentration in the tumor and the presence or absence of EGFRvIII mutation in patients treated with this drug.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive oral erlotinib once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 6 patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 8 patients are treated at that dose level.

Patients are followed at 4 weeks, every 12 weeks for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 6-20 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 confirmed squamous cell carcinoma of the head and neck

    • Stage III, IVA, or IVB
  • Must have completed cisplatin- or carboplatin-based chemoradiotherapy within the past 4-12 weeks

    • Prior radiotherapy must have been given with a radical intent with receipt of at least 90% of planned dose
  • No evidence of disease or presence of inoperable minimal residual disease, defined by 1 of the following:

    • Complete response at primary tumor site and nodes (with or without nodal surgery after chemoradiotherapy)
    • Negative lymph node status (by physical or radiological exam) AND persistent tumefaction less than 25% of original tumor size or residual mass due to scarring
  • Tumor tissue samples available for EGFRvIII mutation analysis
  • No known brain metastasis

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • ECOG 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Absolute granulocyte count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • ALT/AST < 2 times upper limit of normal (ULN)
  • Bilirubin < ULN (unless due to Gilbert's syndrome)

Renal

  • Creatinine < 1.5 times ULN

Cardiovascular

  • No myocardial infarction within the past year
  • No cardiac ventricular arrhythmias requiring medication
  • No history of cardiac disease
  • No uncontrolled high blood pressure
  • No unstable angina
  • No congestive heart failure

Ophthalmic

  • No history of severe dry eye syndrome, Sjögren's syndrome, or keratoconjunctivitis sicca
  • No severe exposure keratopathy
  • No abnormal slit-lamp examination using a vital dye (e.g., fluorescein or Bengal-Rose)
  • No abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • No disorder that might increase the risk for epithelium-related complication (e.g., bullous keratopathy, aniridia, severe chemical burns, or neutrophilic keratitis)
  • No congenital abnormality (e.g., Fuch's dystrophy)
  • No ocular inflammation or infection

Gastrointestinal

  • Able to take oral medication
  • No gastrointestinal (GI) tract disease requiring IV alimentation
  • No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
  • No active peptic ulcer disease

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious active infection
  • No other serious underlying medical condition that would preclude study participation
  • No prior allergic reaction to compounds of similar chemical or biological composition to erlotinib
  • No other malignancy with the past 5 years except adequately treated non-melanoma skin cancer (unless in the same area treated with radical radiotherapy) or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics
  • Recovered from prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics
  • Recovered from prior radiotherapy

Surgery

  • See Disease Characteristics
  • No prior surgical procedure affecting absorption
  • No concurrent ophthalmic surgery

Other

  • More than 4 weeks since other prior investigational drugs
  • No other concurrent investigational agents
  • No other concurrent anticancer therapy
  • Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased vigilance with respect to INR
  • Concurrent nasogastric or gastrostomy tube feeding for dysphagia allowed provided there is no evidence of significant residual mucositis (i.e., > grade 1)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00079053

Locations
Canada, Ontario
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Canada, Quebec
Hopital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
Sponsors and Collaborators
National Cancer Institute of Canada
Investigators
Study Chair: Denis Soulieres, MD, MSC CHUM - Hotel Dieu Hospital
  More Information

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

Study ID Numbers: CDR0000353485, CAN-NCIC-HN5, ROCHE-CAN-NCIC-HN5
Study First Received: March 8, 2004
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00079053  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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 III squamous cell carcinoma of the paranasal sinus and nasal cavity
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
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
salivary gland squamous cell carcinoma
stage III salivary gland cancer
stage IV salivary gland cancer

Study placed in the following topic categories:
Erlotinib
Squamous cell carcinoma
Carcinoma
Epidermoid carcinoma
Nasopharyngeal carcinoma
Head and Neck Neoplasms
Carcinoma, squamous cell
Laryngeal carcinoma
Hypopharyngeal cancer
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Salivary Gland Diseases
Carcinoma, squamous cell of head and neck
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009