Loco-regional Esophageal Cancer
Conditions
Brief summary
The purpose of this study is to determine whether bevacizumab can improve the outcome of treatment for patients with esophageal cancer whose disease is confined to the esophagus or the closely surrounding lymph nodes.
Detailed description
Standard treatment is pre-operative chemotherapy and radiation, followed by surgery. In this study, bevacizumab will be added to the pre-operative chemotherapy and radiation, and then bevacizumab will also be administered for a year after surgery. Bevacizumab is a humanized monoclonal antibody (a type of protein that is normally made by the immune system to help defend the body from infection and cancer) produced by Genentech, Inc. using recombinant DNA technology. Bevacizumab has been approved by the FDA for the treatment of metastatic colorectal cancer in combination with chemotherapy. Bevacizumab is experimental in the treatment of esophageal cancer and has not been approved by the FDA for the treatment of esophageal cancer. Bevacizumab is an antibody directed against vascular endothelial growth factor, or VEGF. VEGF is a growth factor with a well defined role in normal and abnormal blood vessel formation. It is present in a wide variety of normal tissues, but is produced in excess by most solid cancers (tumors). In the setting of cancer, VEGF promotes the growth of blood vessels that bring nutrients to tumor cells. In studies with laboratory animals, bevacizumab inhibits the growth of several different types of human cancer cells, including colon cancer cells, by blocking the effects of VEGF. By blocking VEGF, your doctors hope that bevacizumab may decrease blood supply to the tumor, and therefore decrease the ability of the tumor to grow and come back after chemotherapy, radiation, and surgery.
Interventions
DRUGBevacizumab
Pre-Operative Treatment: Bevacizumab will be given over 60-90 minutes through an I.V. catheter on days # 2 and 16. Post-Operative Treatment:Bevacizumab given over 60-90 minutes through an I.V. catheter every 21 days for 12 months, starting 6-8 weeks after surgery.
DRUGPaclitaxel
Pre-Operative Chemotherapy treatment: Paclitaxel 45 mg/m2 will be administered as a 1-hour intravenous infusion on days #2, 9, 16, 23, and 30. It will be given before cisplatin administration.
DRUGCisplatin
Pre-Operative Chemotherapy Treatment: Cisplatin 30 mg/m2 over 1 hour on days #2, 9, 16, 23, and 30. It will be given after paclitaxel.
DRUG5-Fluorouracil
Pre-Operative Chemotherapy Treatment: 5-Fluorouracil at 200 mg/m2/day will be given as a continuous intravenous infusion on days #2-33.
RADIATIONRadiation Therapy
Pre-Operative Treatment: Radiotherapy will be given Monday through Friday five days a week on days 1-5, 8-12, 15-19, 22-26, and 29-33. Radiotherapy will be administered using MV x-rays. CT scans, the barium swallow, the endoscopy and endoscopic ultrasound reports and PET scans should be used for tumor definition. Post-Operative Radiotherapy: In the event that gross residual disease is left behind at the time of surgery or the patient is found to have a microscopic positive deep or gastric margin following surgery, additional treatment with radiation therapy will be considered.
PROCEDUREEsophagectomy
Transhiatal esophagectomy performed on approximately Day #57 (6 weeks after last dose of bevacizumab.)
Sponsors
Genentech, Inc.
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. No prior treatment for esophageal cancer 2. No prior radiation to the chest or upper abdominal area 3. No prior treatment with an EGFR inhibitor or an anti-angiogenic agent 4. Disease should be limited to the esophagus and regional lymph nodes -
Exclusion criteria
1. History of stroke 2. History of heart attack 3. Inadequately controlled high blood pressure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival Time | 5 years | The primary outcome that will be measured is the length of time that patients are alive without recurrence of cancer following this therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients Cancer Free at the Time of Surgery | 1 year | Determination of whether the pre-operative treatment can eliminate all the cancer cells at the time of surgery. |
| The Proportion of Toxicities Experienced by Participants | Every three weeks for one year | To assess the toxicity of this regimen. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bevacizumab Bevacizumab: Pre-Operative Treatment: Bevacizumab will be given over 60-90 minutes through an I.V. catheter on days 2 and 16. Post-Operative Treatment:Bevacizumab given over 60-90 minutes through an I.V. catheter every 21 days for 12 months, starting 6-8 weeks after surgery.
Paclitaxel: Pre-Operative Chemotherapy treatment: Paclitaxel 45 mg/m\^2 will be administered as a 1-hour intravenous infusion on days 2, 9, 16, 23, and 30. It will be given before cisplatin administration.
Cisplatin: Pre-Operative Chemotherapy Treatment: Cisplatin 30 mg/m\^2 over 1 hour on days 2, 9, 16, 23, and 30. It will be given after paclitaxel.
5-Fluorouracil: Pre-Operative Chemotherapy Treatment: 5-Fluorouracil at 200 mg/m2/day will be given as a continuous intravenous infusion on days #2-33.
Radiation Therapy: Pre-Operative Treatment: Radiotherapy will be given Monday through Friday five days a week on days 1-5, 8-12, 15-19, 22-26, and 29-33. Radiotherapy will be administered using MV x-rays. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | Bevacizumab |
|---|---|
| Age, Continuous | 60 years |
| 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 | 4 / 6 |
Outcome results
Primary
Disease Free Survival Time
The primary outcome that will be measured is the length of time that patients are alive without recurrence of cancer following this therapy.
Time frame: 5 years
Population: The study was unable to accrue the number of patients necessary to analyze the primary objective.
Secondary
The Number of Patients Cancer Free at the Time of Surgery
Determination of whether the pre-operative treatment can eliminate all the cancer cells at the time of surgery.
Time frame: 1 year
Population: The study was unable to accrue the number of patients necessary to analyze the objective.
Secondary
The Proportion of Toxicities Experienced by Participants
To assess the toxicity of this regimen.
Time frame: Every three weeks for one year
Population: The study was unable to accrue the number of patients necessary to analyze the objective.