Esophageal Cancer
Conditions
Keywords
adenocarcinoma of the esophagus, recurrent esophageal cancer, squamous cell carcinoma of the esophagus, stage IV esophageal cancer
Brief summary
RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well gefitinib works in treating patients with recurrent or metastatic esophageal or gastroesophageal junction cancer.
Detailed description
OBJECTIVES: Primary * Explore the activity of single agent gefitinib, in terms of response rate, in a patient population with recurrent or metastatic esophageal or gastroesophageal junction cancer. Secondary * Assess the toxicity of this drug in these patients. OUTLINE: Patients are stratified according to prior treatment (yes vs no). Patients receive oral gefitinib once daily for at least 8 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for survival. PROJECTED ACCRUAL: A total of 76 patients will be accrued for this study.
Interventions
DRUGZD1839
ZD1839 treatment will be taken once a day PO, every day about the same time
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
NA
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: * Pathologically confirmed squamous cell carcinoma, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus or gastroesophageal junction * Patients must have disease that is either metastatic (i.e., M1b by the definitions of the American Joint Committee on Cancer 1997 staging system) or recurrent after definitive therapy, and must be considered incurable by conventional treatments * Patients with small cell, or mixed small cell/non-small-cell histology are ineligible * Patients with lymphoma or sarcoma are also ineligible * Disease must be measurable in at least one dimension by physical exam, x-ray, CT scan or MRI, ultrasound, or endoscopy * Measurable disease can be a previously irradiated lesion if disease growth has been documented in the lesion since completion of radiation therapy * An elevation in carcinoembryonic antigen (CEA) is not sufficient to use by itself in response assessment PATIENT CHARACTERISTICS: * ECOG Performance Status 0-1 * WBC ≥ 3,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Creatinine ≤ 2.0 mg/dL * Alkaline phosphatase and AST \< twice normal * Bilirubin \< twice normal * Calcium normal * No known severe hypersensitivity to study drug or any of its excipients * No clinical evidence of any other uncontrolled malignancy except adequately treated basal or squamous cell skin cancer or in situ cervical cancer * Pregnant or nursing women are ineligible * Fertile patients must use effective contraception * No evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) * No evidence of clinically active interstitial lung disease * Patients with chronic stable radiographic changes who are asymptomatic need not be excluded PRIOR CONCURRENT THERAPY: * Patients may not have received more than one previous systemic treatment regimen * Systemic treatment may have been given as part of definitive (adjuvant, neoadjuvant, concurrent, or sequential) management or for metastatic or recurrent disease * Previously untreated patients are also eligible * No previous treatment with study drug or any other epidermal growth factor receptor (EGFR) antagonists * More than 30 days since prior treatment with a non-approved or investigational drug * At least 4 weeks must have elapsed since any surgery, radiation therapy, or chemotherapy administration * Recovered from previous oncologic or other major surgery * No concurrent barbiturates (e.g., phenytoin), carbamazepine, rifampicin, phenobarbital or Hypericum perforatum (St. John's wort) * No concurrent surgery, radiation therapy, hormonal therapy, or other chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients With Complete or Partial Response Rate of Single Agent ZD1839 in a Patient Population With Recurrent or Metastatic Cancer of the Esophagus or Gastroesophageal Junction, Using the RECIST 1.0 Criteria. | at 8 weeks after initiation of treatment | The overall response is the number of patients with the best response recorded in measurable disease (target lesions) from start to disease progression.Complete response is the number of patients with the disappearance of all target lesions. Partial response is the number of patients with larger than or equal to 30% decrease in sum of the longest diameters from baseline. Progressive disease is larger than or equal to 20% increase in sum of the longest diameters over the smallest sum observed or appearance of new lesions. Stable disease is neither PR nor PD criteria met. |
Countries
United States
Participant flow
Recruitment details
Subjects recruited from April 2003 to January 2010 from medical clinic
Participants by arm
| Arm | Count |
|---|---|
| No Prior Chem Therapy Patients receive oral gefitinib once daily for at least 8 weeks in the absence of disease progression or unacceptable toxicity. | 18 |
| Prior Chemotherapy Patients may not have received more than one previous systemic treatment regimen. Systemic treatment may have been given as part of definitive (adjuvant, neoadjuvant, concurrent, or sequential) management or for metastatic or recurrent disease. Patients receive oral gefitinib once daily for at least 8 weeks in the absence of disease progression or unacceptable toxicity. | 40 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | No Prior Chem Therapy | Prior Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 66 years | 58 years | 60 years |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 15 Participants | 33 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 18 | 33 / 40 |
| serious Total, serious adverse events | 4 / 18 | 4 / 40 |
Outcome results
Primary
The Number of Patients With Complete or Partial Response Rate of Single Agent ZD1839 in a Patient Population With Recurrent or Metastatic Cancer of the Esophagus or Gastroesophageal Junction, Using the RECIST 1.0 Criteria.
The overall response is the number of patients with the best response recorded in measurable disease (target lesions) from start to disease progression.Complete response is the number of patients with the disappearance of all target lesions. Partial response is the number of patients with larger than or equal to 30% decrease in sum of the longest diameters from baseline. Progressive disease is larger than or equal to 20% increase in sum of the longest diameters over the smallest sum observed or appearance of new lesions. Stable disease is neither PR nor PD criteria met.
Time frame: at 8 weeks after initiation of treatment
Population: All patients enrolled were analyzed
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| No Prior Therapy | The Number of Patients With Complete or Partial Response Rate of Single Agent ZD1839 in a Patient Population With Recurrent or Metastatic Cancer of the Esophagus or Gastroesophageal Junction, Using the RECIST 1.0 Criteria. | 1 participants |
| Prior Chemotherapy | The Number of Patients With Complete or Partial Response Rate of Single Agent ZD1839 in a Patient Population With Recurrent or Metastatic Cancer of the Esophagus or Gastroesophageal Junction, Using the RECIST 1.0 Criteria. | 3 participants |
Comparison: In patients with prior chemotherapy, \>25% response indicates efficacy and \<10% indicates lack of efficacy. In patients with no prior chemotherapy, \>45% response indicates efficacy and \<25% indicates lack of efficacy. Using a 5% significance level, the study was designed to have 80% power to test each hypothesis.p-value: <0.05binomial test for a single proportion