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

Head and Neck Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00352105
• Other study ID #: CCF5842
• Secondary ID: P30CA043703CCF-5
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 13, 2006
• Last updated: November 1, 2012
• Start date: April 2006
• Est. completion date: May 2010

Study information

• Verified date: November 2012
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: May 2010
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• cisplatin
20mg/m2/d IV continuous infusion x4 days
• fluorouracil
1000mg.m2/d IV continuous x 4 days
• Iressa
250mg/PO qd x 2 years

Radiation:
• hyperfractionated radiation therapy
120cGy bid

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
David Adelstein	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	Number of Participants Who Completed 2 Years of Therapy		at 2 years after start of treatment	Yes