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

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

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: cisplatin; Drug: fluorouracil; Drug: Iressa; Radiation: hyperfractionated radiation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Concurrent Chemotherapy and ZD1839	Drug: cisplatin; 20mg/m2/d IV continuous infusion x4 days; Other Names: CDDP; Drug: fluorouracil; 1000mg.m2/d IV continuous x 4 days; Other Names: 5FU; Drug: Iressa; 250mg/PO qd x 2 years; Other Names: ZD1839; Radiation: hyperfractionated radiation therapy; 120cGy bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Treated With ZD1839 With Chemotherapy and Hyperfractionated Radiation That Had a 1-year Survival	To explore the activity of ZD1839 with chemotherapy and hyperfractionated radiation using 1-year survival	at 1 year after start of treatment
Number of Participants With No Distant Metastatic Disease at 1 Year	1-year distant metastatic disease control in patients with locally advanced squamous cell head and neck cancer. Distant disease means that cancer came back in sites outside of the head and neck.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With No Local Disease at 1 Year	Number of Participants with No Local Disease at 1 Year. Local disease means that the cancer came back in the same site.	at 1 year after start of treatment
Number of Patients With Greater Than or Equal to Mild (Grade 1) Toxicity	Any toxicity greater than or equal to Grade 1= mild	at 1 year after start of treatment
Number of Patients With a Complete Response Defined as Complete Disappearance of All Clinically Detectable Tumor.	Complete response rate per RECIST Criteria (CTC V3)	3 years
Number of Participants Who Completed 2 Years of Therapy		at 2 years after start of treatment

Collaborators and Investigators

• Sponsor: David Adelstein
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: David J. Adelstein, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: July 13, 2006
• First Submitted That Met QC Criteria: July 13, 2006
• First Posted (Estimate): July 14, 2006

Study Record Updates

• Last Update Posted (Estimate): November 4, 2012
• Last Update Submitted That Met QC Criteria: November 1, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: 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; 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
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil
• Other Study ID Numbers: CCF5842; P30CA043703 (U.S. NIH Grant/Contract); CCF-5842 (Other Identifier: Cleveland Clinic IRB); ZENECA-1839/0235