Head and Neck Cancer
Conditions
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
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.
Interventions
DRUGcisplatin
20mg/m2/d IV continuous infusion x4 days
DRUGfluorouracil
1000mg.m2/d IV continuous x 4 days
DRUGIressa
250mg/PO qd x 2 years
RADIATIONhyperfractionated radiation therapy
120cGy bid
Sponsors
National Cancer Institute (NCI)
David Adelstein
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Treated With ZD1839 With Chemotherapy and Hyperfractionated Radiation That Had a 1-year Survival | at 1 year after start of treatment | To explore the activity of ZD1839 with chemotherapy and hyperfractionated radiation using 1-year survival |
| Number of Participants With No Distant Metastatic Disease at 1 Year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With No Local Disease at 1 Year | at 1 year after start of treatment | Number of Participants with No Local Disease at 1 Year. Local disease means that the cancer came back in the same site. |
| Number of Patients With Greater Than or Equal to Mild (Grade 1) Toxicity | at 1 year after start of treatment | Any toxicity greater than or equal to Grade 1= mild |
| Number of Patients With a Complete Response Defined as Complete Disappearance of All Clinically Detectable Tumor. | 3 years | Complete response rate per RECIST Criteria (CTC V3) |
| Number of Participants Who Completed 2 Years of Therapy | at 2 years after start of treatment | — |
Countries
United States
Participant flow
Recruitment details
Patients accrued between April 2003 and December 2007 from clinical facility
Participants by arm
| Arm | Count |
|---|---|
| 5-FU, Cisplatin, Radiation and Iressa Patients undergo hyperfractionated radiotherapy twice daily, 5 days a week, beginning on day 1 and continuing for 6 weeks. Patients also receive fluorouracil IN continuously over 96 hrs. and cisplatin IV continuously over 96 hrs. on days 1-3 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. | 60 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 19 |
| Overall Study | Death | 5 |
| Overall Study | Lack of Efficacy | 9 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | 5-FU, Cisplatin, Radiation and Iressa |
|---|---|
| Age Continuous | 57 years STANDARD_DEVIATION 8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 58 Participants |
| Region of Enrollment United States | 60 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 55 / 60 |
| serious Total, serious adverse events | 60 / 60 |
Outcome results
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.
Time frame: 1 year
Population: 5 early deaths were not evaluable
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| 5-FU, Cisplatin, Radiation and Iressa | Number of Participants With No Distant Metastatic Disease at 1 Year | 54 participants | 2 |
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
Time frame: at 1 year after start of treatment
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| 5-FU, Cisplatin, Radiation and Iressa | Number of Patients Treated With ZD1839 With Chemotherapy and Hyperfractionated Radiation That Had a 1-year Survival | 52 participants | 4 |
Secondary
Number of Participants Who Completed 2 Years of Therapy
Time frame: at 2 years after start of treatment
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| 5-FU, Cisplatin, Radiation and Iressa | Number of Participants Who Completed 2 Years of Therapy | 20 participants | 7 |
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.
Time frame: at 1 year after start of treatment
Population: 5 early deaths not evaluable
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| 5-FU, Cisplatin, Radiation and Iressa | Number of Participants With No Local Disease at 1 Year | 48 participants | 3 |
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)
Time frame: 3 years
Population: 5 early deaths were not evaluable
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5-FU, Cisplatin, Radiation and Iressa | Number of Patients With a Complete Response Defined as Complete Disappearance of All Clinically Detectable Tumor. | 42 participants |
Secondary
Number of Patients With Greater Than or Equal to Mild (Grade 1) Toxicity
Any toxicity greater than or equal to Grade 1= mild
Time frame: at 1 year after start of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5-FU, Cisplatin, Radiation and Iressa | Number of Patients With Greater Than or Equal to Mild (Grade 1) Toxicity | 60 participants |