Clinical trial NCT00352105: Cisplatin, Fluorouracil, Iressa, and Radiation Therapy Patients With Locally Advanced Head and Neck Cancer
Official title: A Phase I/II Trial of Concurrent Chemotherapy and ZD1839 (IRESSA) With Hyperfractionated Radiation Therapy, Followed by Maintenance ZD1839 (IRESSA) for Patients With Locally Advanced Squamous Cell Head and Neck Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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 IV squamous cell 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 squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-07-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as cisplatin and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cisplatin, fluorouracil, and gefitinib together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects of giving cisplatin, fluorouracil, and gefitinib together with hyperfractionated radiation therapy and to see how well they work in treating patients with locally advanced head and neck cancer.

Detailed description: OBJECTIVES:

Primary

* Explore the activity of cisplatin, fluorouracil, gefitinib, and hyperfractionated radiotherapy, in terms of 1-year survival and 1-year distant metastatic disease control, in patients with locally advanced squamous cell carcinoma of the head and neck.

Secondary

* Explore the activity of this regimen, in terms of disease-specific survival and local control, in these patients.
* Assess the toxicity of this regimen in these patients.
* Assess the complete response rate in patients treated with this regimen.
* Assess the toxicity and tolerability of long-term maintenance with gefitinib in patients rendered disease free after this treatment regimen.

OUTLINE: Patients undergo hyperfractionated radiotherapy twice daily, 5 days a week, beginning on day 1 and continuing for 6 weeks. Patients also receive fluorouracil IV continuously over 96 hours and cisplatin IV continuously over 96 hours on days 1-4 and 22-25 and oral gefitinib beginning once daily on day 1 and continuing for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed primary\* squamous cell carcinoma of the head and neck region, excluding any of the following:

  * Nasopharynx
  * Paranasal sinuses
  * Salivary glands NOTE: \*Primary site must be identified
* Locoregionally confined stage III or IV disease

  * No evidence of nodal disease below the clavicles
  * No distant hematogenous metastases (M0)

PATIENT CHARACTERISTICS:

* ECOG performance status 0-1
* WBC \> 3,500/mm³
* Platelet count \> 100,000/mm³
* Creatinine ≤ 2.0 mg/dL
* Alkaline phosphatase \< 2 times normal
* AST \< 2 times normal
* Bilirubin ≤ 2.0 mg/dL
* Calcium normal
* Not pregnant or nursing
* Fertile patients must use effective contraception
* Must not be a poor compliance risk for follow-up
* No known severe hypersensitivity to gefitinib or any excipients of this drug
* No evidence of clinically active interstitial lung disease

  * Patients with chronic, stable radiographic changes who are asymptomatic are eligible
* No unstable or uncontrolled angina, clinically apparent jaundice, or active infection
* No history of any other malignancy (except squamous cell or basal cell skin cancer or cervical carcinoma in situ) unless disease free for ≥ 5 years
* No other severe, uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)

PRIOR CONCURRENT THERAPY:

* Recovered from prior oncologic or other major surgery
* No prior definitive surgery, radiotherapy, chemotherapy, immunotherapy, or epidermal growth factor receptor inhibitors for head and neck cancer
* No investigational drugs within the past 30 days
* No concurrent CYP3A4 inducers, including any of the following:

  * Phenytoin
  * Carbamazepine
  * Rifampin
  * Phenobarbital
  * Hypericum perforatum (St. John's wort)
* Concurrent surgery allowed provided gefitinib is not administered 2 weeks before and 2 weeks after surgery
* No concurrent aminoglycoside antibiotics

Primary outcomes:
measure: Number of Patients Treated With ZD1839 With Chemotherapy and Hyperfractionated Radiation That Had a 1-year Survival
timeFrame: at 1 year after start of treatment
measure: Number of Participants With No Distant Metastatic Disease at 1 Year
timeFrame: 1 year
Secondary outcomes:
measure: Number of Participants With No Local Disease at 1 Year
timeFrame: at 1 year after start of treatment
measure: Number of Patients With Greater Than or Equal to Mild (Grade 1) Toxicity
timeFrame: at 1 year after start of treatment
measure: Number of Patients With a Complete Response Defined as Complete Disappearance of All Clinically Detectable Tumor.
timeFrame: 3 years
measure: Number of Participants Who Completed 2 Years of Therapy
timeFrame: at 2 years after start of treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: David J. Adelstein, MD
role: STUDY_CHAIR
References: