Chemotherapy, Radiation Therapy, and Cetuximab Followed by Surgery, Docetaxel, and Cetuximab in Treating Patients With Esophageal Cancer or Gastroesophageal Junction Cancer
- Conditions
- Esophageal Cancer
- Interventions
- Procedure: SurgeryRadiation: Radiotherapy
- Registration Number
- NCT00551759
- Lead Sponsor
- Eastern Cooperative Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving docetaxel and cetuximab after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This phase II trial is studying how well giving chemotherapy and radiation therapy together with cetuximab followed by surgery, docetaxel and cetuximab works in treating patients with esophageal cancer or gastroesophageal junction cancer.
- Detailed Description
OBJECTIVES:
Primary
* To determine the pathologic complete response (pCR) rate of neoadjuvant chemoradiotherapy with OX/5-FU/radiotherapy (RT) plus cetuximab in patients with resectable adenocarcinoma of the esophagus.
Secondary
* To evaluate the safety of neoadjuvant chemoradiotherapy with OX/5-FU/RT plus cetuximab in patients with resectable adenocarcinoma of the esophagus.
* To evaluate the safety and tolerability of adjuvant therapy comprising cetuximab and docetaxel in these patients.
* To carry out exploratory studies to determine if activity of this regimen correlates with epidermal growth factor receptor (EGFR)-related genetic and pathway activation markers and circulating endothelial and tumor cells.
OUTLINE: This is a multicenter study.
* Neoadjuvant chemoradiotherapy and cetuximab: Patients receive oxaliplatin intravenously (IV) over 2 hours on days 1, 15, and 29, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, and 5-FU IV continuously over 24 hours on days 1-35. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Patients then proceed to surgery.
* Surgery: Patients undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Patients with an R0 or R1 resection proceed to adjuvant therapy. Patients whose tumors have not been completely resected or who have metastatic disease discontinue protocol therapy and receive further therapy at the discretion of the treating physician.
* Adjuvant therapy: Within 4-8 weeks after surgery, patients receive docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 2 years, and then every 6 months for 3-5 years.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 22
- Newly diagnosed adenocarcinoma of the esophagus (> 20 cm below the incisors) or gastroesophageal (GE) junction, untreated with chemotherapy, radiation therapy, and surgery. Endoscopy with biopsy and dilation was permitted.
- Tumor stage T2N0M0, T3N0M0, T1-3N+M0, or T1-3N0-1M1A as determined by imaging studies performed no greater than 4 weeks prior to registration, and biopsy, where appropriate. Celiac nodal metastasis (M1A disease) was permitted if other eligibility criteria were met. Data from endoscopic ultrasound and endoscopy were required for staging. The following imaging was required: CT scan with IV contrast and PET or PET+CT. If the PET/CT incorporates CT with IV contrast, then a separate CT is not required. If laparoscopy or other relevant procedures were performed, the data were to be incorporated into stage assignment. Any lesion suspicious for metastasis had to have been biopsied to prove eligibility.
- Tumor extension into cardia, if present, must have been no more than 2 cm.
- Tumors must have been considered surgically resectable (T1-3, not T4).
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Granulocytes > 1,000/ mm³
- Platelets > 100,000 μL
- Creatinine normal or creatinine clearance > 60 mL/min
- Total serum bilirubin < 1.5 mg/dL
- Fertile patients must use effective contraception
- History of a curatively treated malignancy from which the patient has been disease-free for ≥ 2 years and has a survival prognosis of > 5 years
-
Pregnant or breast-feeding.
-
Prior severe infusion reaction to a monoclonal antibody
-
prior therapy specifically and directly targeting the epidermal growth factor receptor (EGFR) pathway
-
Hypertension
-
Uncontrolled diabetes
-
Intercurrent illness that would likely interfere with protocol therapy or prevent surgical resection
-
Any of the following within the past 6 months:
- New York Heart Association class III-IV congestive heart failure
- Cerebrovascular accident or transient ischemic attack
- Unstable angina or myocardial infarction
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Neoadjuvant therapy, Surgery, adjuvant therapy Surgery Neoadjuvant chemoradiotherapy and cetuximab: Patients (pts) receive oxaliplatin IV over 2 hours on days 1, 15, and 29, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, and 5-FU IV over 24 hours on days 1-35. Pts also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Pts then proceed to surgery. Surgery: Pts undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Pts with an R0 or R1 resection proceed to adjuvant therapy. Pts whose tumors have not been completely resected or who have metastatic disease discontinue protocol therapy and receive further therapy at the discretion of the treating physician. Adjuvant therapy: Within 4-8 weeks after surgery, pts receive docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Neoadjuvant therapy, Surgery, adjuvant therapy Radiotherapy Neoadjuvant chemoradiotherapy and cetuximab: Patients (pts) receive oxaliplatin IV over 2 hours on days 1, 15, and 29, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, and 5-FU IV over 24 hours on days 1-35. Pts also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Pts then proceed to surgery. Surgery: Pts undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Pts with an R0 or R1 resection proceed to adjuvant therapy. Pts whose tumors have not been completely resected or who have metastatic disease discontinue protocol therapy and receive further therapy at the discretion of the treating physician. Adjuvant therapy: Within 4-8 weeks after surgery, pts receive docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Neoadjuvant therapy, Surgery, adjuvant therapy 5-Fluorouracil Neoadjuvant chemoradiotherapy and cetuximab: Patients (pts) receive oxaliplatin IV over 2 hours on days 1, 15, and 29, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, and 5-FU IV over 24 hours on days 1-35. Pts also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Pts then proceed to surgery. Surgery: Pts undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Pts with an R0 or R1 resection proceed to adjuvant therapy. Pts whose tumors have not been completely resected or who have metastatic disease discontinue protocol therapy and receive further therapy at the discretion of the treating physician. Adjuvant therapy: Within 4-8 weeks after surgery, pts receive docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Neoadjuvant therapy, Surgery, adjuvant therapy Oxaliplatin Neoadjuvant chemoradiotherapy and cetuximab: Patients (pts) receive oxaliplatin IV over 2 hours on days 1, 15, and 29, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, and 5-FU IV over 24 hours on days 1-35. Pts also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Pts then proceed to surgery. Surgery: Pts undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Pts with an R0 or R1 resection proceed to adjuvant therapy. Pts whose tumors have not been completely resected or who have metastatic disease discontinue protocol therapy and receive further therapy at the discretion of the treating physician. Adjuvant therapy: Within 4-8 weeks after surgery, pts receive docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Neoadjuvant therapy, Surgery, adjuvant therapy Docetaxel Neoadjuvant chemoradiotherapy and cetuximab: Patients (pts) receive oxaliplatin IV over 2 hours on days 1, 15, and 29, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, and 5-FU IV over 24 hours on days 1-35. Pts also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Pts then proceed to surgery. Surgery: Pts undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Pts with an R0 or R1 resection proceed to adjuvant therapy. Pts whose tumors have not been completely resected or who have metastatic disease discontinue protocol therapy and receive further therapy at the discretion of the treating physician. Adjuvant therapy: Within 4-8 weeks after surgery, pts receive docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Neoadjuvant therapy, Surgery, adjuvant therapy Cetuximab Neoadjuvant chemoradiotherapy and cetuximab: Patients (pts) receive oxaliplatin IV over 2 hours on days 1, 15, and 29, cetuximab IV over 1-2 hours on days 1, 8, 15, 22, and 29, and 5-FU IV over 24 hours on days 1-35. Pts also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33. Pts then proceed to surgery. Surgery: Pts undergo surgical resection within 4-8 weeks after completion of neoadjuvant chemoradiotherapy and cetuximab. Pts with an R0 or R1 resection proceed to adjuvant therapy. Pts whose tumors have not been completely resected or who have metastatic disease discontinue protocol therapy and receive further therapy at the discretion of the treating physician. Adjuvant therapy: Within 4-8 weeks after surgery, pts receive docetaxel IV over 1 hour on days 1, 8, 15, 22, and 29 and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Proportion of Patients With Pathologic Complete Response At time of surgery (which occurred 63 to 91 days after study entry) After neoadjuvant therapy, participants underwent surgical resection. The excised tumor was examined by a pathologist. A pathologic complete response is defined as the absence of any histopathologic evidence of tumor in the resected esophageal and nodal tissue specimen.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (109)
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States
Hematology and Oncology Associates
🇺🇸Chicago, Illinois, United States
Southwest Medical Center
🇺🇸Liberal, Kansas, United States
Cancer Center of Kansas, PA - Parsons
🇺🇸Parsons, Kansas, United States
Associates in Womens Health, PA - North Review
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Chanute
🇺🇸Chanute, Kansas, United States
Cancer Center of Kansas, PA - Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Dodge City
🇺🇸Dodge City, Kansas, United States
Cancer Center of Kansas, PA - Wichita
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - El Dorado
🇺🇸El Dorado, Kansas, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
Medical X-Ray Center, PC
🇺🇸Sioux Falls, South Dakota, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸Lewes, Delaware, United States
CCOP - Christiana Care Health Services
🇺🇸Newark, Delaware, United States
Overlook Hospital
🇺🇸Summit, New Jersey, United States
CCOP - Wichita
🇺🇸Wichita, Kansas, United States
Via Christi Cancer Center at Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Winfield
🇺🇸Winfield, Kansas, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
Cancer Center of Paoli Memorial Hospital
🇺🇸Paoli, Pennsylvania, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
Fox Chase Virtua Health Cancer Program at Virtua West Jersey
🇺🇸Voorhees, New Jersey, United States
Carol G. Simon Cancer Center at Morristown Memorial Hospital
🇺🇸Morristown, New Jersey, United States
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
🇺🇸Marlton, New Jersey, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸Voorhees, New Jersey, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Marshfield Clinic Cancer Care at Regional Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
UPMC Cancer Centers
🇺🇸Pittsburgh, Pennsylvania, United States
Cancer Resource Center - Lincoln
🇺🇸Lincoln, Nebraska, United States
Summa Center for Cancer Care at Akron City Hospital
🇺🇸Akron, Ohio, United States
Gundersen Lutheran Center for Cancer and Blood
🇺🇸La Crosse, Wisconsin, United States
Pottstown Memorial Regional Cancer Center
🇺🇸Pottstown, Pennsylvania, United States
CCOP - Main Line Health
🇺🇸Wynnewood, Pennsylvania, United States
Center for Cancer Treatment & Prevention at Sacred Heart Hospital
🇺🇸Eau Claire, Wisconsin, United States
Marshfield Clinic - Indianhead Center
🇺🇸Rice Lake, Wisconsin, United States
Marshfield Clinic - Lakeland Center
🇺🇸Minocqua, Wisconsin, United States
Ministry Medical Group at Saint Mary's Hospital
🇺🇸Rhinelander, Wisconsin, United States
Our Lady of Mercy Medical Center Comprehensive Cancer Center
🇺🇸Bronx, New York, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
Minnesota Oncology Hematology, PA - Maplewood
🇺🇸Maplewood, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸Shakopee, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Minnesota Oncology Hematology, PA - Woodbury
🇺🇸Woodbury, Minnesota, United States
Mercy Cancer Center at Mercy Medical Center
🇺🇸Canton, Ohio, United States
St. Luke's Cancer Network at St. Luke's Hospital
🇺🇸Bethlehem, Pennsylvania, United States
Bryn Mawr Hospital
🇺🇸Bryn Mawr, Pennsylvania, United States
Marshfield Clinic - Wausau Center
🇺🇸Wausau, Wisconsin, United States
Marshfield Clinic - Weston Center
🇺🇸Weston, Wisconsin, United States
CCOP - Missouri Valley Cancer Consortium
🇺🇸Omaha, Nebraska, United States
Immanuel Medical Center
🇺🇸Omaha, Nebraska, United States
Alegant Health Cancer Center at Bergan Mercy Medical Center
🇺🇸Omaha, Nebraska, United States
Creighton University Medical Center
🇺🇸Omaha, Nebraska, United States
Saint Joseph's Hospital
🇺🇸Marshfield, Wisconsin, United States
Aultman Cancer Center at Aultman Hospital
🇺🇸Canton, Ohio, United States
Saint Michael's Hospital Cancer Center
🇺🇸Stevens Point, Wisconsin, United States
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Rush-Copley Cancer Care Center
🇺🇸Aurora, Illinois, United States
Decatur Memorial Hospital Cancer Care Institute
🇺🇸Decatur, Illinois, United States
Hinsdale Hematology Oncology Associates
🇺🇸Hinsdale, Illinois, United States
Swedish-American Regional Cancer Center
🇺🇸Rockford, Illinois, United States
Midwest Center for Hematology/Oncology
🇺🇸Joliet, Illinois, United States
Joliet Oncology-Hematology Associates, Limited - West
🇺🇸Joliet, Illinois, United States
North Shore Oncology and Hematology Associates, Limited - Libertyville
🇺🇸Libertyville, Illinois, United States
Cancer Care and Hematology Specialists of Chicagoland - Niles
🇺🇸Niles, Illinois, United States
Hematology Oncology Associates - Skokie
🇺🇸Skokie, Illinois, United States
Regional Cancer Center at Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Carle Cancer Center at Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
McFarland Clinic, PC
🇺🇸Ames, Iowa, United States
Cedar Rapids Oncology Associates
🇺🇸Cedar Rapids, Iowa, United States
Mercy Capitol Hospital
🇺🇸Des Moines, Iowa, United States
CCOP - Iowa Oncology Research Association
🇺🇸Des Moines, Iowa, United States
John Stoddard Cancer Center at Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates at John Stoddard Cancer Center
🇺🇸Des Moines, Iowa, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Mercy Cancer Center at Mercy Medical Center - North Iowa
🇺🇸Mason City, Iowa, United States
McCreery Cancer Center at Ottumwa Regional
🇺🇸Ottumwa, Iowa, United States
Mercy Medical Center - Sioux City
🇺🇸Sioux City, Iowa, United States
St. Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
Cancer Center of Kansas, PA - Newton
🇺🇸Newton, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Cancer Center of Kansas, PA - Kingman
🇺🇸Kingman, Kansas, United States
Cancer Center of Kansas, PA - Pratt
🇺🇸Pratt, Kansas, United States
Union Hospital Cancer Program at Union Hospital
🇺🇸Elkton, Maryland, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
🇺🇸Reading, Pennsylvania, United States
Lankenau Cancer Center at Lankenau Hospital
🇺🇸Wynnewood, Pennsylvania, United States
Hematology and Oncology Associates of Northeastern Pennsylvania
🇺🇸Scranton, Pennsylvania, United States
Marshfield Clinic - Wisconsin Rapids Center
🇺🇸Wisconsin Rapids, Wisconsin, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Medical Oncology and Hematology Associates at Mercy Cancer Center
🇺🇸Des Moines, Iowa, United States
Mercy Cancer Center at Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
John Stoddard Cancer Center at Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
Cancer Center of Kansas, PA - Wellington
🇺🇸Wellington, Kansas, United States
La Grange Oncology Associates - Geneva
🇺🇸Naperville, Illinois, United States
Cancer Center of Kansas, PA - Salina
🇺🇸Salina, Kansas, United States
Saint Anthony Memorial Health Centers
🇺🇸Michigan City, Indiana, United States