Cisplatin, Fluorouracil, Iressa, and Radiation Therapy Patients With Locally Advanced Head and Neck Cancer

David Adelstein

Status and phase: Completed; Phase 2; Phase 1

Conditions: Head and Neck Cancer

Treatments: Drug: cisplatin; Drug: fluorouracil; Drug: Iressa; Radiation: hyperfractionated radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00352105

ZENECA-1839/0235

P30CA043703 (U.S. NIH Grant/Contract)

CCF5842

CCF-5842 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Concurrent Chemotherapy and ZD1839

Experimental group

Treatment:

Drug: Iressa

Radiation: hyperfractionated radiation therapy

Drug: fluorouracil

Drug: cisplatin