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Docetaxel With or Without Gefitinib in Treating Patients With Metastatic or Locally Recurrent Head and Neck Cancer
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00088907
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining docetaxel with gefitinib may kill more tumor cells. It is not yet known whether docetaxel is more effective with or without gefitinib in treating head and neck cancer.

PURPOSE: This randomized phase III trial is studying docetaxel and gefitinib to see how well they work compared to docetaxel alone in treating patients with metastatic or locally recurrent head and neck cancer.


Condition Intervention Phase
Head and Neck Cancer
Drug: docetaxel
Drug: gefitinib
Drug: placebo
Phase III

MedlinePlus related topics: Cancer Head and Neck Cancer Salivary Gland Disorders
Drug Information available for: Docetaxel ZD1839
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double-Blind, Placebo Control
Official Title: Phase III Randomized, Placebo Controlled, Trial Of Docetaxel Versus Docetaxel Plus ZD1839 (Iressa, Gefitinib, NSC 715055) In Performance Status 2 Or Previously Treated Patients With Recurrent Or Metastatic Head And Neck Cancer

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

Primary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • Response rate as measured by RECIST criteria at baseline and every 8 weeks during treatment [ Designated as safety issue: No ]
  • Quality of life as assessed by Functional Assessment of Cancer Therapy (FACT)-Head and Neck and FACT-General at baseline, days 15 and 28 of course 1, and day 28 of each subsequent course [ Designated as safety issue: No ]
  • Correlation of prevalence of pgp, cyp, and epidermal growth factor receptor (EFGR) with response to treatment [ Designated as safety issue: No ]

Estimated Enrollment: 330
Study Start Date: August 2004
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm I: Active Comparator
Patients receive docetaxel IV over 30-60 minutes on days 1, 8, and 15 and oral placebo once daily on days 1-28.
Drug: docetaxel
Given IV over 30-60 minutes
Drug: placebo
Given orally
Arm II: Experimental
Patients receive docetaxel as in arm I and oral gefitinib once daily on days 1-28.
Drug: docetaxel
Given IV over 30-60 minutes
Drug: gefitinib
Given orally

Detailed Description:

OBJECTIVES:

Primary

  • Compare the survival of patients with poor-prognosis metastatic or locally recurrent squamous cell carcinoma of the head and neck treated with docetaxel with vs without gefitinib.

Secondary

  • Compare time to progression and response rate in patients treated with these regimens.
  • Compare quality of life in patients treated with these regimens.
  • Correlate the expression and activation status of the epidermal growth factor receptor (EGFR) signaling pathway with clinical outcome in patients treated with these regimens.
  • Determine the frequency of common polymorphisms of CYP3A and EGFR and the impact of these polymorphisms on survival, time to progression, and response rate in these patients and the toxic effects of these regimens.
  • Analyze docetaxel and ZD1839 (Iressa, gefitinib) pharmacokinetics and to correlate polymorphisms with pharmacokinetic variability, response, toxicity, and other endpoints.
  • Compare disease-related symptoms and overall quality of life in patients treated with these regimens.
  • Determine whether additional clinical benefit associated with gefitinib can be detected as an improvement in patient-reported symptoms in these patients.

OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to treatment with prior chemotherapy (pretreated vs untreated), ECOG performance status (0 vs 1 vs 2), weight loss within the past 6 months (< 5% vs ≥ 5%), and prior cetuximab treatment (yes or no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive docetaxel IV over 30-60 minutes on days 1, 8, and 15 and oral placebo once daily on days 1-28.
  • Arm II: Patients receive docetaxel as in arm I and oral gefitinib once daily on days 1-28.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in arm I who have disease progression may receive single-agent oral gefitinib once daily until further disease progression.

Quality of life is assessed at baseline, on days 15 and 28 of course 1, on day 28 of all subsequent courses, and at 2-4 weeks after completion of study treatment.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 330 patients (165 per treatment arm) will be accrued for this study within 31.5 months.

  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

    • Metastatic or locally recurrent disease
    • No histologic type WHO 2 or 3 nasopharyngeal carcinoma
  • Incurable by local therapies
  • Meets 1 of the following criteria:

    • ECOG 2 AND no prior chemotherapy for metastatic or locally recurrent head and neck cancer
    • ECOG 0-2 AND received prior chemotherapy (i.e., ≥ 1 prior chemotherapy regimen [without docetaxel]) for metastatic or locally recurrent disease OR received prior chemotherapy (without docetaxel) as part of a primary curative therapy within the past 6 months
  • Measurable or non-measurable disease

    • Disease within a previously irradiated field is considered measurable provided there is unequivocal disease progression or biopsy-proven residual carcinoma after radiotherapy

      • Persistent disease after radiotherapy must be biopsy-proven ≥ 8 weeks after completion of radiotherapy
  • No tumors that are unequivocally invading major vessels (e.g. carotid artery)
  • No tumor-related hemorrhagic events in the past 3 months that require major medical intervention (e.g., surgery or embolization)
  • No known brain metastasis

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • See Disease Characteristics

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 8.0 g/dL

Hepatic

  • Alkaline phosphatase AND AST or ALT meeting criteria for 1 of the following:

    • Alkaline phosphatase normal AND AST or ALT ≤ 5 times upper limit of normal (ULN)
    • Alkaline phosphatase ≤ 2.5 times UNL AND AST or ALT ≤ 1.5 times ULN
    • Alkaline phosphatase ≤ 5 times ULN and AST or ALT normal
  • Bilirubin normal

Renal

  • Creatinine < 2.0 mg/dL OR
  • Creatinine clearance > 60 mL/min

Cardiovascular

  • No uncontrolled hypertension
  • No unstable angina
  • No congestive heart failure
  • No serious arrhythmia requiring medication

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • No hypercalcemia related to head and neck cancer
  • No peripheral neuropathy ≥ grade 2
  • No hypersensitivity to gefitinib or any of its excipients
  • No severe hypersensitivity to docetaxel or other drugs formulated with polysorbate 80
  • No unstable systemic disease
  • No active infection
  • No significant traumatic injury within the past 3 weeks
  • No other malignancy within the past 5 years except curatively treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix
  • No other co-existing condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior monoclonal antibody ABX-EBX or monoclonal antibody MDX-447
  • No prior cetuximab

    • Cetuximab given concurrently with radiation or chemoradiotherapy for up to 9 total weekly doses as part of initial potentially curative therapy is allowed provided it was completed more than 6 months prior to study registration
  • At least 2 weeks since prior biologic/targeted therapy
  • No concurrent immunotherapy
  • No concurrent colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy

  • See Disease Characteristics
  • Prior paclitaxel allowed provided there was no disease progression during treatment
  • At least 4 weeks since prior chemotherapy and recovered
  • No prior docetaxel
  • No other concurrent chemotherapy

Endocrine therapy

  • No concurrent antitumor hormonal therapy

    • Concurrent contraceptives, replacement steroids, and dexamethasone allowed

Radiotherapy

  • See Disease Characteristics
  • At least 3 weeks since prior radiotherapy and recovered
  • No concurrent radiotherapy

Surgery

  • At least 3 weeks since prior major surgery and recovered

Other

  • See Disease Characteristics
  • No other prior systemic epidermal growth factor receptor inhibitors, including any of the following:

    • Gefitinib
    • Erlotinib
    • PKI166
    • CI-1033
    • EKB-569
  • No concurrent CYP3A4 inducers, including any of the following:

    • Phenytoin
    • Carbamazepine
    • Rifampin
    • Phenobarbital
    • Hypericum perforatum (St. John's wort)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No concurrent proton pump inhibitors or H2 antagonists within 4 hours after gefitinib administration
  • No concurrent therapeutic anticoagulation
  • No other concurrent antitumor therapy
  • No other concurrent experimental medications
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00088907

  Show 262 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Athanassios Argiris, MD UPMC Cancer Centers
Investigator: Jill Gilbert, MD MBCCOP - LSU Health Sciences Center
  More Information

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

Study ID Numbers: CDR0000377545, ECOG-E1302
Study First Received: August 4, 2004
Last Updated: November 16, 2008
ClinicalTrials.gov Identifier: NCT00088907  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
stage III squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent metastatic squamous neck cancer with occult primary
untreated metastatic squamous neck cancer with occult primary
recurrent salivary gland cancer
salivary gland squamous cell carcinoma
stage III salivary gland cancer
stage IV salivary gland cancer
recurrent squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
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 oropharynx
recurrent squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx

Study placed in the following topic categories:
Squamous cell carcinoma
Recurrence
Carcinoma
Epidermoid carcinoma
Docetaxel
Nasopharyngeal carcinoma
Head and Neck Neoplasms
Metastatic squamous neck cancer with occult primary
Carcinoma, squamous cell
Laryngeal carcinoma
Hypopharyngeal cancer
Carcinoma, Squamous Cell
Gefitinib
Salivary Gland Diseases

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009