Oxaliplatin (NSC-266046) Plus Protracted Infusion 5-Fluorouracil And Radiation For Potentially Curable Esophageal Cancer: A Phase II Trial With Molecular Correlates
18 Years
N/A
Both
Esophageal Cancer
Trial Information
Oxaliplatin (NSC-266046) Plus Protracted Infusion 5-Fluorouracil And Radiation For Potentially Curable Esophageal Cancer: A Phase II Trial With Molecular Correlates
OBJECTIVES:
Primary
- Determine the pathologic complete response probability in patients with stage II or III
adenocarcinoma of the esophagus or gastroesophageal junction treated with neoadjuvant
oxaliplatin, fluorouracil, and radiotherapy followed by definitive surgical resection.
Secondary
- Determine the frequency and severity of toxic effects associated with this neoadjuvant
regimen in these patients.
- Determine the overall survival and progression-free survival of patients treated with
this regimen.
Exploratory Analyses (subject to funding availability)
- Correlate, preliminarily, initial messenger ribonucleic acid (mRNA) levels of the genes
for thymidylate synthase (TS), γ-glutamyl transpeptidase (γGT), γ-glutamyl cysteine
(γ-GCS), DNA excision repair cross-complementing (ERCC-1), and xeroderma pigmentosum
(XPA) with response and survival of patients treated with this regimen.
- Correlate, preliminarily, the mRNA levels of TS, γGT, γ-GCS, ERCC-1, and XPA before and
after treatment with this regimen with survival of these patients.
- Correlate, preliminarily, specific genetic polymorphisms of TS and ERCC-1 with tumor
response and overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter study.
- Neoadjuvant chemoradiotherapy: Patients receive oxaliplatin IV over 2 hours on days 1,
15, and 29 and fluorouracil (5-FU) IV continuously on days 8-43. Beginning on day 8,
patients also undergo radiotherapy once daily, 5 days a week, for 5 weeks.
- Surgery: Patients with stable disease or better undergo surgical resection 4-10 weeks
after completion of chemoradiotherapy.
- Adjuvant chemotherapy: Beginning 4-10 weeks after surgery, patients receive
chemotherapy comprising oxaliplatin IV over 2 hours on days 1, 15, and 29 and 5-FU IV
continuously on days 1-36.
Treatment continues in the absence of unacceptable toxicity or disease progression.
Patients are followed every 3 months for 1 year and then every 6 months for 2 years.
PROJECTED ACCRUAL: A total of 45-85 patients will be accrued for this study within 17-21
months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed primary adenocarcinoma of the thoracic esophagus or
gastroesophageal junction
- No recurrent disease
- Primary esophageal tumor at least 20 cm below the incisors (if < 26 cm below the
incisors, a bronchoscopy must be performed and cytology must be negative)
- Esophageal disease confined to esophagus and peri-esophageal soft tissue
- Gastroesophageal junction disease extending ≤ 2 cm into the gastric cardia
- Clinical stage II or III disease by CT scan or MRI
- If no esophageal mass is detected by these methods, esophageal endoscopic
ultrasound is required to determine stage
- Positron-emission tomography scan is required to confirm stage
- Measurable or non-measurable disease by x-ray, scanning, or physical examination
- No celiac axis nodes ≥ 1.5 cm
- Measurable regional lymph nodes ≥ 1.5 cm at stations 2-10=N1 OR subdiaphragmatic
lymph nodes at stations 15-19 ≤ 1.5 cm by CT scan or MRI allowed
- Palpable supraclavicular lymph nodes must be free of metastatic esophageal
cancer by biopsy
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- Zubrod 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- White blood cell (WBC) count ≥ 3,000/mm^3
- Hemoglobin ≥ 10.0 g/dL (transfusion allowed)
Hepatic
- Albumin ≥ 3 g/dL
- Bilirubin normal
Renal
- Creatinine ≤ 1.5 times upper limit of normal
Cardiovascular
- No myocardial infarction or cerebrovascular event within the past 6 months
Pulmonary
- No active pneumonia or inflammatory lung infiltrate
Other
- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix
- No peripheral neuropathy ≥ grade 2
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy for esophageal cancer
Endocrine therapy
- Not specified
Radiotherapy
- No prior radiotherapy for esophageal cancer
- No concurrent intensity-modulated radiotherapy
Surgery
- No prior surgical resection or attempted surgical resection of esophageal cancer
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathological Complete Response
Outcome Description:
Complete pathologic response assessed after chemoradiotherapy and surgery, defined as no evidence of residual disease on path review. Patients who did not receive surgery are assumed to have not responded.
Outcome Time Frame:
10-16 weeks after beginning study treatment
Safety Issue:
No
Principal Investigator
Lawrence P. Leichman, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Desert Regional Medical Center Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000371963
NCT ID:
NCT00086996
Start Date:
September 2004
Completion Date:
August 2011
Related Keywords:
- Esophageal Cancer
- adenocarcinoma of the esophagus
- stage II esophageal cancer
- stage III esophageal cancer
- Esophageal Diseases
- Esophageal Neoplasms
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| Cardinal Bernardin Cancer Center at Loyola University Medical Center | Maywood, Illinois 60153-5500 |
| Barbara Ann Karmanos Cancer Institute | Detroit, Michigan 48201 |
| CCOP - Upstate Carolina | Spartanburg, South Carolina 29303 |
| CCOP - Wichita | Wichita, Kansas 67214-3882 |
| CCOP - Kansas City | Kansas City, Missouri 64131 |
| CCOP - Bay Area Tumor Institute | Oakland, California 94609-3305 |
| CCOP - Cancer Research for the Ozarks | Springfield, Missouri 65807 |
| CCOP - Montana Cancer Consortium | Billings, Montana 59101 |
| Veterans Affairs Medical Center - Dayton | Dayton, Ohio 45428 |
| CCOP - Dayton | Kettering, Ohio 45429 |
| CCOP - Greenville | Greenville, South Carolina 29615 |
| LDS Hospital | Salt Lake City, Utah 84143 |
| CCOP - Grand Rapids | Grand Rapids, Michigan 49503 |
| Charles M. Barrett Cancer Center at University Hospital | Cincinnati, Ohio 45267-0526 |
| CCOP - Scott and White Hospital | Temple, Texas 76508 |
| USC/Norris Comprehensive Cancer Center and Hospital | Los Angeles, California 90033-0804 |
| CCOP - St. Louis-Cape Girardeau | Saint Louis, Missouri 63141 |
| Veterans Affairs Medical Center - Seattle | Seattle, Washington 98108 |
| Utah Valley Regional Medical Center - Provo | Provo, Utah 84604 |
| University of California Davis Cancer Center | Sacramento, California 95817 |
| Wesley Medical Center | Wichita, Kansas 67214 |
| Mobile Infirmary Medical Center | Mobile, Alabama 36640-0460 |
| Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center | Kansas City, Kansas 66160-7353 |
| Josephine Ford Cancer Center at Henry Ford Hospital | Detroit, Michigan 48202 |
| Swedish Cancer Institute at Swedish Medical Center - First Hill Campus | Seattle, Washington 98104 |
| Hulston Cancer Center at Cox Medical Center South | Springfield, Missouri 65807 |
| St. John's Regional Health Center | Springfield, Missouri 65804 |
| McDowell Cancer Center at Akron General Medical Center | Akron, Ohio 44307 |
| Via Christi Cancer Center at Via Christi Regional Medical Center | Wichita, Kansas 67214 |
| Mission Hospitals - Memorial Campus | Asheville, North Carolina 28801 |
| Saint Anthony's Hospital at Saint Anthony's Health Center | Alton, Illinois 62002 |
| Good Samaritan Regional Health Center | Mt. Vernon, Illinois 62864 |
| Southwest Medical Center | Liberal, Kansas 67901 |
| Battle Creek Health System Cancer Care Center | Battle Creek, Michigan 49017 |
| Holland Community Hospital | Holland, Michigan 49423 |
| Hackley Hospital | Muskegon, Michigan 49443 |
| Munson Medical Center | Traverse City, Michigan 49684 |
| Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital | Gape Girardeau, Missouri 63701 |
| David C. Pratt Cancer Center at St. John's Mercy | St. Louis, Missouri 63141 |
| Northern Rockies Radiation Oncology Center | Billings, Montana 59101 |
| Hematology-Oncology Centers of the Northern Rockies - Billings | Billings, Montana 59101 |
| Big Sky Oncology | Great Falls, Montana 59405 |
| St. Peter's Hospital | Helena, Montana 59601 |
| Kalispell Regional Medical Center | Kalispell, Montana 59901 |
| Glacier Oncology, PLLC | Kalispell, Montana 59901 |
| Montana Cancer Center at St. Patrick Hospital and Health Sciences Center | Missoula, Montana 59802 |
| Montana Cancer Specialists at Montana Cancer Center | Missoula, Montana 59802 |
| Community Medical Center | Missoula, Montana 59801 |
| American Fork Hospital | American Fork, Utah 84003 |
| Logan Regional Hospital | Logan, Utah 84321 |
| Utah Cancer Specialists at UCS Cancer Center | Salt Lake City, Utah 84106 |
| Olympic Hematology and Oncology | Bremerton, Washington 98310 |
| University Cancer Center at University of Washington Medical Center | Seattle, Washington 98195 |
| Harborview Medical Center | Seattle, Washington 98104 |
| Group Health Central Hospital | Seattle, Washington 98104 |
| Cancer Care Northwest - Spokane South | Spokane, Washington 99202 |
| Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center | Savannah, Georgia 31403-3089 |
| Lucille P. Markey Cancer Center at University of Kentucky | Lexington, Kentucky 40536-0093 |
| Butterworth Hospital at Spectrum Health | Grand Rapids, Michigan 49503-2560 |
| Decatur Memorial Hospital Cancer Care Institute | Decatur, Illinois 62526 |
| Eden Medical Center | Castro Valley, California 94546 |
| Alta Bates Summit Medical Center - Summit Campus | Oakland, California 94609 |
| Valley Care Medical Center | Pleasanton, California 94588 |
| Poudre Valley Hospital | Fort Collins, Colorado 80524 |
| St. Francis Hospital and Health Centers - Beech Grove Campus | Beech Grove, Indiana 46107 |
| Cancer Center of Kansas, PA - Dodge City | Dodge City, Kansas 67801 |
| St. Francis Comprehensive Cancer Center | Topeka, Kansas 66606 |
| Mecosta County Medical Center | Big Rapids, Michigan 49307 |
| Saint Francis Medical Center | Cape Girardeau, Missouri 63701 |
| Samaritan North Cancer Care Center | Dayton, Ohio 45415 |
| Grandview Hospital | Dayton, Ohio 45405 |
| David L. Rike Cancer Center at Miami Valley Hospital | Dayton, Ohio 45409 |
| Good Samaritan Hospital | Dayton, Ohio 45406 |
| Blanchard Valley Medical Associates | Findlay, Ohio 45840 |
| Charles F. Kettering Memorial Hospital | Kettering, Ohio 45429 |
| Middletown Regional Hospital | Middletown, Ohio 45044 |
| UVMC Cancer Care Center at Upper Valley Medical Center | Troy, Ohio 45373-1300 |
| Ruth G. McMillan Cancer Center at Greene Memorial Hospital | Xenia, Ohio 45385 |
| Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center | Kingsport, Tennessee 37662 |
| Dixie Regional Medical Center - East Campus | Saint George, Utah 84770 |
| Minor and James Medical, PLLC | Seattle, Washington 98104 |
| Polyclinic First Hill | Seattle, Washington 98122 |
| Welch Cancer Center at Sheridan Memorial Hospital | Sheridan, Wyoming 82801 |
| Highland General Hospital | Oakland, California 94602 |
| Northeast Georgia Medical Center | Gainesville, Georgia 30501 |
| Randolph Hospital | Asheboro, North Carolina 27203 |
| Moses Cone Regional Cancer Center at Wesley Long Community Hospital | Greensboro, North Carolina 27401 |
| Annie Penn Cancer Center | Reidsville, North Carolina 27320 |
| Reid Hospital & Health Care Services | Richmond, Indiana 47374 |
| Cancer Center of Kansas, PA - Chanute | Chanute, Kansas 66720 |
| Cancer Center of Kansas, PA - El Dorado | El Dorado, Kansas 67042 |
| Cancer Center of Kansas, PA - Kingman | Kingman, Kansas 67068 |
| Cancer Center of Kansas, PA - Newton | Newton, Kansas 67114 |
| Cancer Center of Kansas, PA - Parsons | Parsons, Kansas 67357 |
| Cancer Center of Kansas, PA - Pratt | Pratt, Kansas 67124 |
| Cancer Center of Kansas, PA - Salina | Salina, Kansas 67401 |
| Cotton-O'Neil Cancer Center | Topeka, Kansas 66606 |
| Cancer Center of Kansas, PA - Wellington | Wellington, Kansas 67152 |
| Cancer Center of Kansas, PA - Wichita | Wichita, Kansas 67214 |
| Associates in Womens Health, PA - North Review | Wichita, Kansas 67208 |
| Cancer Center of Kansas, PA - Medical Arts Tower | Wichita, Kansas 67208 |
| Cancer Center of Kansas, PA - Winfield | Winfield, Kansas 67156 |
| Billings Clinic - Downtown | Billings, Montana 59107-7000 |
| Bozeman Deaconess Cancer Center | Bozeman, Montana 59715 |
| St. James Healthcare Cancer Care | Butte, Montana 59701 |
| Great Falls Clinic - Main Facility | Great Falls, Montana 59405 |
| Sletten Cancer Institute at Benefis Healthcare | Great Falls, Montana 59405 |
| Kalispell Medical Oncology at KRMC | Kalispell, Montana 59901 |
| Clinton Memorial Hospital | Wilmington, Ohio 45177 |
| Sandra L. Maxwell Cancer Center | Cedar City, Utah 84720 |
| Jon and Karen Huntsman Cancer Center at Intermountain Medical Center | Murray, Utah 84157 |
| Val and Ann Browning Cancer Center at McKay-Dee Hospital Center | Ogden, Utah 84403 |
| Southwest Virginia Regional Cancer Center at Wellmonth Health | Norton, Virginia 24273 |
| St. Joseph Cancer Center | Bellingham, Washington 98225 |
| Columbia Basin Hematology | Kennewick, Washington 99336 |
| Wenatchee Valley Medical Center | Wenatchee, Washington 98801-2028 |
| Regional Cancer Center at Memorial Medical Center | Springfield, Illinois 62781-0001 |
| Good Samaritan Cancer Center at Good Samaritan Hospital | Kearney, Nebraska 68848-1990 |
| Tucker Center for Cancer Care at Orange Regional Medical Center | Middletown, New York 10940-4199 |
| Rutherford Hospital | Rutherfordton, North Carolina 28139 |
| Gibbs Regional Cancer Center at Spartanburg Regional Medical Center | Spartanburg, South Carolina 29303 |
| St. John's Regional Medical Center | Joplin, Missouri 64804 |
| Providence Cancer Center | Anchorage, Alaska 99508 |
| Highlands Oncology Group - Springdale | Springdale, Arkansas 72764 |
| Lacks Cancer Center at Saint Mary's Health Care | Grand Rapids, Michigan 49503 |
| Metro Health Hospital | Grand Rapids, Michigan 49506 |
| Guardian Oncology and Center for Wellness | Missoula, Montana 59804 |
| Rockwood Clinic Cancer Treatment Center | Spokane, Washington 99204-2967 |
| Doctors Medical Center - San Pablo Campus | San Pablo, California 94806 |
| Boston University Cancer Research Center | Boston, Massachusetts 02118 |
| St. Vincent Healthcare Cancer Care Services | Billings, Montana 59101 |
| Desert Regional Medical Center Comprehensive Cancer Center | Palm Springs, California 92262 |
| East Bay Radiation Oncology Center | Castro Valley, California 94546 |
| Larry G Strieff MD Medical Corporation | Oakland, California 94609 |
| Tom K Lee, Incorporated | Oakland, California 94609 |
| Bay Area Breast Surgeons, Incorporated | Oakland, California 94609 |
| Valley Medical Oncology Consultants - Pleasanton | Pleasanton, California 94588 |
| AnMed Cancer Center | Anderson, South Carolina 29621 |
| Valley Medical Oncology Consultants - Castro Valley | Castro Valley, California 94546 |
| Valley Medical Oncology | Fremont, California 94538 |
| Olathe Cancer Center | Olathe, Kansas 66061 |
| Frontier Cancer Center | Great Falls, Montana 59405 |
