Esophageal Diseases, Esophageal Neoplasms
Conditions
Keywords
Esophagus, Esophagogastric Junction, Avastin, Bevacizumab, Erlotinib
Brief summary
Determine the time to progression for the combination of erlotinib and bevacizumab in patients with previously treated metastatic cancer of the esophagus or gastroesophageal junction
Detailed description
We postulate that the addition of bevacizumab may increase the efficacy of erlotinib in patients with metastatic esophageal cancer, without adding significant toxicity. The non-overlapping toxicity profiles may allow the administration of the maximum tolerated doses for both agents without additive toxicities with the goal of demonstrating synergistic clinical activity. This combination has been previously tested in two studies for other malignancies with good tolerance and encouraging results.
Interventions
DRUGErlotinib
DRUGAvastin
Sponsors
Washington University School of Medicine
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
* Biopsy proven adenocarcinoma or squamous cell carcinoma of the esophagus or gastroesophageal junction. * Metastatic or advanced inoperable disease previously treated with one prior chemotherapy regimen * Age greater than 18 years. * Performance status ECOG 0 to 1. * Adequate hepatic and renal function, defined as: * Serum creatinine \<= 3.0 mg/dL; * Creatinine clearance \>= 45 mL/min. * Bilirubin \<= 1.5 x institutional normal; * ALT/AST \<= 3 x institutional normal. * Patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension. The longest diameter of measurable lesions must be \>= 20 mm with conventional techniques or \>= 10 mm with spiral CT scan. Lesions that are not considered measurable include: bone lesions, leptomeningeal disease, brain lesions, ascites, pericardial or pleural effusion, and tumors situated in a previously irradiated area. * Use of effective means of contraception for both male and female patients with child-bearing potential. * A 1 month wash-out period is required for all patients entering this study from a previous treatment regimen
Exclusion criteria
* Previous use of anti-EGFR or anti-VEGF therapy. * Previous history of cancer. The patient with a prior malignancy is eligible for this study only if the patient meets the following criteria for a cancer survivor. A cancer survivor is eligible provided the following criteria are met: (1) patient has undergone potentially curative therapy for all prior malignancies, (2) patients have been considered disease free for at least 5 years (with the exception of basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix). * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to day 0; or anticipation of the need for major surgical procedure during the course of the study. (In the case of high risk procedures such as liver resection, thoracotomy, or neurosurgery, it is recommended that patient delay treatment with chemotherapy for at least 6 weeks and with bevacizumab at least 8 weeks after surgery). * Radiation therapy within the last 2 weeks. * Presence of central nervous system or brain metastases at any time. * Serious, non-healing wound, ulcer, or bone fracture * History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0; and/or minor surgical procedures such as fine needle aspiration or core biopsies within 7 days prior to day 0. * Presence of coagulopathy or clinical history of significant hematemesis, melena, or hemoptysis related to the diagnosis of esophageal cancer. * Previous history of deep venous thrombosis or thromboembolic disease. * Urine protein/urine creatinine ratio ≥ 1.0 at screening. * Pregnant or lactating. * Unstable angina or history of myocardial infarction within the last 6 months. * History of stroke within the last 6 months. * Uncontrolled hypertension with blood pressure persistently \> 150/100 mmHg despite optimal antihypertensive therapy. * Clinically significant peripheral vascular disease. * Congestive heart failure with New York Heart Association grades III or IV (see appendix B). * Inability to complete the study and follow-up procedures. * Participation in therapeutic clinical trials or currently receiving other investigational treatment(s) within 30 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | Median follow-up for TTP 6 weeks (6-18 weeks) | * TTP is defined as the time from initiation of treatment to the date of documented progression. * The median of TTP with 95% confidence interval will be presented. * Progressive disease (target lesions) is defined as at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. * Progressive disease (non-target lesions) is defined as appearance of one or more new lesions. Unequivocal progression of existing non-target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Rate (OS) | Median followup time from completion of treatment 325.5 days (44-401 days) | OS is defined as the time from initiation of treatment to the date of death for any reason. |
| Response Rate (Complete Response (CR), Partial Response (PR), and CR+PR) | Median follow-up for response 6 weeks (6-18 weeks) | * CR = disappearance of all target lesions * PR = at least a 30% decrease in the sum of the LD of the target lesions taking as reference the baseline sum LD. |
| Incidence and Severity of Toxicities | Median follow-up time for toxicities 72 days (72 days-156 days) | Grade 3 and higher toxicities using CTCAE Version 3.0. |
Countries
United States
Participant flow
Recruitment details
The study opened to participant accrual on 03/16/2007 and closed to participant accrual on 01/21/2009.
Participants by arm
| Arm | Count |
|---|---|
| Erlotinib and Avastin Patients will be treated with erlotinib 150 mg oral daily and Avastin 15 mg/kg intravenously each cycle of therapy (each cycle is 21 days or every 3 weeks). The first infusion of Avastin will be administered over 90 minutes. If tolerated, the second infusion will be given over 60 minutes and in 30 minutes for the subsequent treatments. Treatment will be administered until disease progression or intolerable side effects. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Erlotinib and Avastin |
|---|---|
| Age, Continuous | 63.5 years |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 |
Outcome results
Primary
Time to Progression (TTP)
* TTP is defined as the time from initiation of treatment to the date of documented progression. * The median of TTP with 95% confidence interval will be presented. * Progressive disease (target lesions) is defined as at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. * Progressive disease (non-target lesions) is defined as appearance of one or more new lesions. Unequivocal progression of existing non-target lesions.
Time frame: Median follow-up for TTP 6 weeks (6-18 weeks)
Population: 1 participant was not analyzed because the participant was removed from study during the first cycle due to an adverse event and was considered not evaluable for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib and Avastin | Time to Progression (TTP) | 4.2 months |
Secondary
Incidence and Severity of Toxicities
Grade 3 and higher toxicities using CTCAE Version 3.0.
Time frame: Median follow-up time for toxicities 72 days (72 days-156 days)
Population: Details of all SAEs and AEs are listed in the Serious Adverse Events and Other Adverse Events modules.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib and Avastin | Incidence and Severity of Toxicities | Coagulation: Other, IVC Clot | 1 participants |
| Erlotinib and Avastin | Incidence and Severity of Toxicities | Death - Disease Progression NOS | 1 participants |
| Erlotinib and Avastin | Incidence and Severity of Toxicities | Diarrhea | 1 participants |
| Erlotinib and Avastin | Incidence and Severity of Toxicities | GI: Abdominal hemorrhage, NOS | 1 participants |
| Erlotinib and Avastin | Incidence and Severity of Toxicities | Pneumonia | 1 participants |
| Erlotinib and Avastin | Incidence and Severity of Toxicities | Hypernatremia | 1 participants |
| Erlotinib and Avastin | Incidence and Severity of Toxicities | Confusion | 1 participants |
Secondary
Overall Survival Rate (OS)
OS is defined as the time from initiation of treatment to the date of death for any reason.
Time frame: Median followup time from completion of treatment 325.5 days (44-401 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib and Avastin | Overall Survival Rate (OS) | 10.7 months |
Secondary
Response Rate (Complete Response (CR), Partial Response (PR), and CR+PR)
* CR = disappearance of all target lesions * PR = at least a 30% decrease in the sum of the LD of the target lesions taking as reference the baseline sum LD.
Time frame: Median follow-up for response 6 weeks (6-18 weeks)
Population: 1 participant was not analyzed because the participant was removed from study during the first cycle due to an adverse event and was considered not evaluable for this outcome.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib and Avastin | Response Rate (Complete Response (CR), Partial Response (PR), and CR+PR) | Complete response | 0 participants |
| Erlotinib and Avastin | Response Rate (Complete Response (CR), Partial Response (PR), and CR+PR) | Partial response | 0 participants |