Esophageal Cancer
Conditions
Keywords
adenocarcinoma of the esophagus, recurrent esophageal cancer, stage IV esophageal cancer
Brief summary
RATIONALE: Biological therapies such as cetuximab may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase II trial is studying how well cetuximab works in treating patients with metastatic esophageal cancer or gastroesophageal junction cancer.
Detailed description
OBJECTIVES: * Determine the 6-month overall survival of patients with metastatic adenocarcinoma of the esophagus or gastroesophageal junction treated with cetuximab as second-line therapy. * Determine the response rate (confirmed and unconfirmed, complete and partial), time to progression, and time to treatment failure in patients treated with this drug. * Determine the toxicity of this drug in these patients. * Correlate, preliminarily, gene expression and germline polymorphism of enzymes and genes involved in the epidermal growth factor receptor pathway, DNA repair, and angiogenesis with time to progression, response, overall survival, toxic effects, and time to treatment failure in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours on day 1. Treatment repeats once weekly in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months until 3 years from the date of study registration. PROJECTED ACCRUAL: A total of 30-55 patients will be accrued for this study within 6-14 months.
Interventions
BIOLOGICALcetuximab
1 time Cetuximab 400mg/m2 IV over 120 minutes followed by weekly Cetuximab 250mg/m2 IV over 60 minutes.
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of 1 of the following sites: * Thoracic esophagus, located \> 20 cm\* from the incisors * Gastroesophageal junction, located ≤ 2 cm into the gastric cardia NOTE: \*Tumors located \< 26 cm from the incisors must be confirmed by bronchoscopy and negative cytology * Disease confined to the esophagus and periesophageal soft tissue * Metastatic disease * Measurable disease by x-ray, scanning, or physical examination * Received exactly 1 prior chemotherapy regimen for metastatic or recurrent disease * One prior adjuvant or neoadjuvant chemotherapy regimen allowed if administered at the time of initial diagnosis with localized disease * No known brain metastases PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * Granulocyte count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Not specified Renal * Creatinine ≤ 1.5 times upper limit of normal Other * No prior allergic reaction to chimerized or murine monoclonal antibodies * No evidence of human anti-mouse antibodies (HAMA) * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission * Not pregnant or nursing * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy * No prior cetuximab Chemotherapy * See Disease Characteristics * At least 4 weeks since prior chemotherapy and recovered * No concurrent chemotherapy Endocrine therapy * Not specified Radiotherapy * At least 4 weeks since prior radiotherapy and recovered Surgery * At least 3 weeks since prior thoraco-abdominal surgery and recovered Other * No other prior therapy that specifically targets the epidermal growth factor pathway * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival at 6 Months | every 3 weeks while on treatment, then every 3 months | Time to death is measured from date of registration to date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Treatment Failure | every 3 weeks while on treatment | Time to treatment failure is measured from date of registration to date of first observation of progressive disease, death due to any cause, symptomatic deterioration, or early discontinuation of treatment. Progressive disease is defined as one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. |
| Time to Progression | every 3 weeks while on treatment, then every 3 months for 3 years | Progression free survival is measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progressive disease is defined as one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab 250 mg/m\^2 on days 1, 8, 15, and 22 of every 28-day cycle. | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Death | 4 |
| Overall Study | Ineligible | 8 |
| Overall Study | Lack of Efficacy | 42 |
| Overall Study | Not protocol specified | 5 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cetuximab |
|---|---|
| Age, Continuous | 61.2 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 54 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 52 / 55 |
| serious Total, serious adverse events | 1 / 55 |
Outcome results
Primary
Overall Survival at 6 Months
Time to death is measured from date of registration to date of death due to any cause.
Time frame: every 3 weeks while on treatment, then every 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cetuximab | Overall Survival at 6 Months | 36 percentage of participants |
Secondary
Time to Progression
Progression free survival is measured from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progressive disease is defined as one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time frame: every 3 weeks while on treatment, then every 3 months for 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab | Time to Progression | 1.8 months |
Secondary
Time to Treatment Failure
Time to treatment failure is measured from date of registration to date of first observation of progressive disease, death due to any cause, symptomatic deterioration, or early discontinuation of treatment. Progressive disease is defined as one or more of the following: 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Death due to disease without prior documentation of progression and without symptomatic deterioration. Symptomatic deterioration is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time frame: every 3 weeks while on treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cetuximab | Time to Treatment Failure | 1.8 months |