A Randomized Phase II Pilot Study Prospectively Evaluating Treatment for Patients Based on ERCC1(Excision Repair Cross-Complementing 1) for Advanced/Metastatic Esophageal, Gastric or Gastroesophageal Junction (GEJ) Cancer
Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil,
irinotecan hydrochloride, and docetaxel, work in different ways to stop the growth of tumor
cells, either by killing the cells or by stopping them from dividing. Combining more than one
drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy
is more effective in treating tumor cells.
PURPOSE: This randomized phase II trial studies how well oxaliplatin, leucovorin calcium, and
fluorouracil work compared to irinotecan hydrochloride and docetaxel in treating patients
with esophageal cancer, gastric cancer, or gastroesophageal junction cancer.
Detailed Description
OBJECTIVES:
- To assess progression-free survival of high-excision repair cross-complementing 1(ERCC1)
patients with advanced or metastatic cancer of the esophagus, stomach, or
gastroesophageal junction (GEJ) treated with FOLFOX comprising oxaliplatin, leucovorin
calcium, and fluorouracil compared to those treated with irinotecan hydrochloride plus
docetaxel.
- To assess progression-free survival of low-ERCC1 patients with advanced or metastatic
cancer of the esophagus, stomach, or GEJ treated with FOLFOX compared to those treated
with irinotecan hydrochloride plus docetaxel.
- To assess progression-free survival of low-ERCC1 patients with advanced or metastatic
cancer of the esophagus, stomach, or GEJ treated with FOLFOX compared to high-ERCC1
patients treated with FOLFOX.
- To assess overall survival of and toxicities in each of the two treatment arms in this
group of patients.
- To assess the response probability (confirmed and unconfirmed, complete and partial
responses) in the subset of patients with measurable disease in each of the two
treatment arms.
- To explore whether there is evidence of interaction between treatment arm and ERCC1
expression in this group of patients. (Exploratory)
- To bank tissue and blood for future translational medicine studies; a) To explore the
relationship of ERCC-1 and ERCC-2 single nucleotide polymorphism (SNP) genotypes with
clinical outcome in these patients; and b) To explore the association between germline
variations in these SNPs and ERCC-1 mRNA expression in these patients. (Exploratory)
OUTLINE: This is a multicenter study. Patients are stratified according to ERCC1 expression
(high [≥ 1.7] vs low [< 1.7]), and disease site (esophageal vs gastric/gastroesophageal
junction). Patients are randomized to 1 of 2 treatment arms.
- Arm I (FOLFOX): Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV
over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-2. Courses repeat
every 14 days in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive irinotecan hydrochloride IV over 90 minutes and docetaxel IV
over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.
Blood and tumor tissue samples may be collected for ERCC1 expression analysis and future
research studies.
After completion of study treatment, patients are followed up every 3 months for up to 3
years.
Phase
Phase 2 - takes the treatment one step further, assessing the activity of a particular therapy in a disease, often building upon leads from the Phase I trial. While patients are generally required to be previously untreated, participation in a Phase II trial doesn't usually preclude the patient from getting the standard treatment after they've received the investigational agent. At best they are allowed to get a new drug they wouldn't be able to get otherwise that may turn out to be better for their disease.Inclusion and Exclusion Criteria
- Patients must have unresectable advanced or metastatic histologically or cytologically confirmed adenocarcinoma of the esophagus, stomach, or gastroesophageal junction (GEJ)
- Patients must not have received treatment for metastatic or unresectable disease
- Patients must not have brain metastases
- Patients must have measurable and/or non-measurable disease
- Patients who have had HER-2 expression testing prior to patient consent to this study must be HER-2 negative; if HER-2 expression has not been tested prior to patient consent to this study, a second specimen must be submitted for HER-2 expression; if the specimen is HER-2 positive (or if HER-2 could not be evaluated), the patient will not be randomized
- Patients must have completed any prior neoadjuvant and adjuvant therapy for resectable disease at least 180 days prior to registration PATIENT CHARACTERISTICS:
- Zubrod performance status of 0-1
- Hemoglobin ≥ 9 g/dL
- Absolute neutrophil count (ANC) ≥ 1,500/mcL
- Platelets ≥ 100,000/mcL
- Total bilirubin ≤ 1.5 mg/dL regardless of whether patients have liver involvement secondary to tumor
- AST and ALT both ≤ 3 times institutional upper limit of normal (IULN) unless the liver is involved with tumor, in which case both AST and ALT must be ≤ 5 times IULN
- Serum creatinine < 1.5 mg/dL within 28 days prior to registration AND/OR calculated creatinine clearance > 60 mL/min
- Patients must not have motor or sensory neuropathy > Grade 1 using CTCAE version 4.0
- Patients must not be pregnant or nursing; women and men of reproductive potential must have agreed to use an effective contraceptive method
- No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for five years PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- All palliative radiation therapy alone must be completed at least 14 days prior to registration
- Patient must have no plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of therapy for treatment of cancer while on this protocol treatment
Sites
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California
- University of California Medical Center At Irvine-Orange Campus, Orange, California, 92868
- Memorial Medical Center, Modesto, California, 95355
- Palo Alto Medical Foundation-Santa Cruz, Santa Cruz, California, 95065
- Palo Alto Medical Foundation-Camino Division, Mountain View, California, 94040
- Palo Alto Medical Foundation-Gynecologic Oncology, Mountain View, California, 94040
- Palo Alto Medical Foundation Health Care, Palo Alto, California, 94301
- Valley Medical Oncology Consultants, Pleasanton, California, 94588
- California Pacific Medical Center-Pacific Campus, San Francisco, California, 94118
- Palo Atlo Medical Foundation-Sunnyvale, Sunnyvale, California, 94806
- University of California at Davis Cancer Center, Sacramento, California, 95817
- Sutter General Hospital, Sacramento, California, 95816
- Sutter Solano Medical Center/Cancer Center, Vallejo, California, 94589
- Sutter Roseville Medical Center, Roseville, California, 95661
- Sutter Davis Hospital, Davis, California, 95616
- Sutter Auburn Faith Hospital, Auburn, California, 95602
- Tahoe Forest Cancer Center, Truckee, California, 96161
- Fremont - Rideout Cancer Center, Marysville, California, 95901
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Colorado
- Mercy Medical Center, Durango, Colorado, 81301
- Front Range Cancer Specialists, Fort Collins, Colorado, 80528
-
New Mexico
- University of New Mexico, Albuquerque, New Mexico, 87106
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Idaho
- Idaho Urologic Institute-Meredian, Meridian, Idaho, 83642
- Saint Alphonsus Cancer Care Center-Boise, Boise, Idaho, 83706
- Saint Joseph Regional Medical Center, Lewiston, Idaho, 83501
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Washington
- Compass Oncology Vancouver, Vancouver, Washington, 98684
- Multicare Health System, Tacoma, Washington, 98415
- Capital Medical Center, Olympia, Washington, 98507
- Providence Regional Cancer System-Lacey, Lacey, Washington, 98503
- Good Samaritan Community Hospital, Puyallup, Washington, 98372
- Saint Clare Hospital, Lakewood, Washington, 98499
- Northwest CCOP, Tacoma, Washington, 98405
- Northwest Medical Specialties PLLC, Tacoma, Washington, 98405
- Saint Joseph Medical Center, Tacoma, Washington, 98405
- Allenmore Hospital, Tacoma, Washington, 98405
- Auburn Regional Medical Center, Auburn, Washington, 98001
- Saint Francis Hospital, Federal Way, Washington, 98003
- Rockwood Clinic, Spokane, Washington, 99220
- Evergreen Hematology and Oncology PS, Spokane, Washington, 99218
- Overlake Hospital Medical Center, Bellevue, Washington, 98004
- Minor and James Medical PLLC, Seattle, Washington, 98104
- Group Health, Seattle, Washington, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington, 98109
- Cascade Cancer Center, Kirkland, Washington, 98034
- Providence Regional Cancer Partnership, Everett, Washington, 98201
-
Montana
- Big Sky Oncology, Great Falls, Montana, 59405
-
Kansas
- Saint Catherine Hospital, Garden City, Kansas, 67846
- Hays Medical Center, Hays, Kansas, 67601
- Saint Rose Ambulatory and Surgery Center, Great Bend, Kansas, 67530
- Cancer Center of Kansas - McPherson, McPherson, Kansas, 67460
- Salina Regional Health Center, Salina, Kansas, 67401
- Cancer Center of Kansas-Manhattan, Manhattan, Kansas, 66502
- Newman Regional Health, Emporia, Kansas, 66801
- Saint Francis Hospital and Medical Center - Topeka, Topeka, Kansas, 66606
- Via Christi Hospital-Pittsburg, Pittsburg, Kansas, 66762
- Kansas City Cancer Center-West, Kansas City, Kansas, 66112
- University of Kansas Medical Center, Kansas City, Kansas, 66160
- Kansas City Cancer Centers-Southwest, Overland Park, Kansas, 66210
- Kansas City CCOP, Prairie Village, Kansas, 66208
-
South Dakota
- Rapid City Regional Hospital, Rapid City, South Dakota, 57701
-
Oklahoma
- Oklahoma Oncology Inc, Tulsa, Oklahoma, 74104
- Natalie Warren Bryant Cancer Center at Saint Francis, Tulsa, Oklahoma, 74136
- Warren Cancer Research Foundation, Tulsa, Oklahoma, 74136
- Tulsa Cancer Institute, Tulsa, Oklahoma, 74146
-
Iowa
- Mercy Medical Center-Sioux City, Sioux City, Iowa, 51104
- Saint Luke's Regional Medical Center, Sioux City, Iowa, 51104
- McFarland Clinic PC-Jefferson, Jefferson, Iowa, 50129
- McFarland Clinic PC-Trinity Cancer Center, Fort Dodge, Iowa, 50501
- McFarland Clinic PC-Boone, Boone, Iowa, 50036
- McFarland Clinic PC-William R Bliss Cancer Center, Ames, Iowa, 50010
- Mary Greeley Medical Center, Ames, Iowa, 50010
- McFarland Clinic PC-Marshalltown, Marshalltown, Iowa, 50158
- Genesis Medical Center - East Campus, Davenport, Iowa, 52803
- Hematology Oncology Associates-Quad Cities, Bettendorf, Iowa, 52722
- Constantinou, Costas L MD (UIA Investigator), Bettendorf, Iowa, 52722
-
Missouri
- Freeman Health System, Joplin, Missouri, 64804
- Saint Joseph Oncology Inc, Saint Joseph, Missouri, 64507
- Kansas City Cancer Centers - North, Kansas City, Missouri, 64154
- Saint Luke's Cancer Institute, Kansas City, Missouri, 64111
- Kansas City Cancer Center - South, Kansas City, Missouri, 64131
- Truman Medical Center, Kansas City, Missouri, 64108
- Kansas City Cancer Center-Lee's Summit, Lee's Summit, Missouri, 64064
- Central Care Cancer Center-Carrie J Babb Cancer Center, Bolivar, Missouri, 65613
- Ozark Health Ventures LLC-Cancer Research for The Ozarks Springfield, Springfield, Missouri, 65804
- Capital Region Medical Center-Goldschmidt Cancer Center, Jefferson City, Missouri, 65109
- Saint John's Clinic-Rolla-Cancer and Hematology, Rolla, Missouri, 65401
- Phelps County Regional Medical Center, Rolla, Missouri, 65401
- Saint Louis-Cape Girardeau CCOP, Saint Louis, Missouri, 63141
- Comprehensive Cancer Care PC, Saint Louis, Missouri, 63141
- Saint John's Mercy Medical Center, Saint Louis, Missouri, 63141
- Missouri Baptist Medical Center, Saint Louis, Missouri, 63131
- Saint Louis Cancer and Breast Institute-South City, Saint Louis, Missouri, 63109
- Southeast Cancer Center, Cape Girardeau, Missouri, 63703
-
Texas
- Baylor College of Medicine, Houston, Texas, 77030
- Ben Taub General Hospital, Houston, Texas, 77030
- Veterans Administration Medical Center, Houston, Texas, 77030
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North Dakota
- Altru Cancer Center, Grand Forks, North Dakota, 58201
-
Arkansas
- University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205
-
Illinois
- Memorial Hospital, Carthage, Illinois, 62321
- Mcdonough District Hospital, Macomb, Illinois, 61455
- Saint Anthony's Health, Alton, Illinois, 62002
- Porubcin, Michael MD (UIA Investigator), Moline, Illinois, 61265
- Spector, David MD (UIA Investigator), Moline, Illinois, 61265
- Trinity Medical Center, Moline, Illinois, 61265
- Garneau, Stewart C MD (UIA Investigator), Moline, Illinois, 61265
- Illinois CancerCare-Havana, Havana, Illinois, 62644
- Mason District Hospital, Havana, Illinois, 62644
- Graham Hospital Association, Canton, Illinois, 61520
- Illinois Oncology Research Association CCOP, Peoria, Illinois, 61615
- Perry Memorial Hospital, Princeton, Illinois, 61356
- Eureka Hospital, Eureka, Illinois, 61530
- Illinois CancerCare-Spring Valley, Spring Valley, Illinois, 61362
- Central Illinois CCOP, Decatur, Illinois, 62526
- Community Cancer Center Foundation, Normal, Illinois, 61761
- Illinois CancerCare-Community Cancer Center, Normal, Illinois, 61761
- Bromenn Regional Medical Center, Normal, Illinois, 61761
- Swedish American Hospital, Rockford, Illinois, 61104
- SwedishAmerican Regional Cancer Center/ACT, Rockford, Illinois, 61107
- Hematology Oncology Consultants Limited, Naperville, Illinois, 60540
- Presence Saint Mary's Hospital, Kankakee, Illinois, 60901
- Adventist La Grange Memorial Hospital, La Grange, Illinois, 60525
- North Shore Hematology Oncology, Libertyville, Illinois, 60048
- Loyola University Medical Center, Maywood, Illinois, 60153
- Illinois Cancer Specialists-Niles, Niles, Illinois, 60714
- Hematology Oncology Associates of Illinois-Highland Park, Highland Park, Illinois, 60035
- Hematology Oncology Associates of Illinois - Skokie, Skokie, Illinois, 60076
- University of Illinois, Chicago, Illinois, 60612
- Hematology and Oncology Associates, Chicago, Illinois, 60611
- Northwestern University, Chicago, Illinois, 60611
-
Wisconsin
- Marshfield Clinic Cancer Center at Sacred Heart, Eau Claire, Wisconsin, 54701
- Sacred Heart Hospital, Eau Claire, Wisconsin, 54701
- Marshfield Clinic-Rice Lake Center, Rice Lake, Wisconsin, 54868
- Lakeview Medical Center-Marshfield Clinic, Rice Lake, Wisconsin, 54868
- Marshfield Clinic, Marshfield, Wisconsin, 54449
- Saint Joseph's Hospital, Marshfield, Wisconsin, 54449
- University of Wisconsin Hospital and Clinics, Madison, Wisconsin, 53792
- Riverview Hospital, Wisconsin Rapids, Wisconsin, 54494
- Marshfield Clinic - Wisconsin Rapids Center, Wisconsin Rapids, Wisconsin, 54494
- Marshfield Clinic Cancer Care at Saint Michael's Hospital, Stevens Point, Wisconsin, 54481
- Saint Michael's Hospital, Stevens Point, Wisconsin, 54481
- Aspirus Regional Cancer Center, Wausau, Wisconsin, 54401
- Saint Clare's Hospital, Weston, Wisconsin, 54476
- Marshfield Clinic - Weston Center, Weston, Wisconsin, 54476
- Marshfield Clinic-Minocqua Center, Minocqua, Wisconsin, 54548
- Marshfield Clinic at James Beck Cancer Center, Rhinelander, Wisconsin, 54501
- Saint Mary's Hospital, Rhinelander, Wisconsin, 54501
- Langlade Hospital and Cancer Center, Antigo, Wisconsin, 54409
- Froedtert and the Medical College of Wisconsin, Milwaukee, Wisconsin, 53226
- Green Bay Oncology Limited at Saint Mary's Hospital, Green Bay, Wisconsin, 54303
- Saint Mary's Hospital, Green Bay, Wisconsin, 54303
- Green Bay Oncology - Oconto Falls, Oconto Falls, Wisconsin, 54154
- Saint Vincent Hospital, Green Bay, Wisconsin, 54301
- Saint Nicholas Hospital, Sheboygan, Wisconsin, 53081
- Holy Family Memorial Hospital, Manitowoc, Wisconsin, 54221
- Bay Area Medical Center, Marinette, Wisconsin, 54143
- Green Bay Oncology - Sturgeon Bay, Sturgeon Bay, Wisconsin, 54235
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Louisiana
- Ochsner Health Center-Summa, Baton Rouge, Louisiana, 70809
- Ochsner Medical Center Jefferson, New Orleans, Louisiana, 70121
- Ochsner Baptist Medical Center, New Orleans, Louisiana, 70115
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Alabama
- University of South Alabama Mitchell Cancer Institute, Mobile, Alabama, 36688
-
Michigan
- Green Bay Oncology - Iron Mountain, Iron Mountain, Michigan, 49801
- Lakeland Community Hospital, Niles, Michigan, 49120
- Green Bay Oncology - Escanaba, Escanaba, Michigan, 49431
- Grand Rapids Clinical Oncology Program, Grand Rapids, Michigan, 49503
- Spectrum Health Big Rapids Hospital, Big Rapids, Michigan, 49307
- Sparrow Hospital, Lansing, Michigan, 48912
- Allegiance Health, Jackson, Michigan, 49201
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Indiana
- IU Health La Porte Hospital, La Porte, Indiana, 46350
- Franciscan Saint Francis Health-Indianapolis, Indianapolis, Indiana, 46237
- Community Howard Regional Health, Kokomo, Indiana, 46904
- Memorial Hospital of South Bend, South Bend, Indiana, 46601
- South Bend Clinic, South Bend, Indiana, 46617
- Cancer Care Partners LLC, Mishawaka, Indiana, 46545
- Memorial Regional Cancer Center Day Road, Mishawaka, Indiana, 46544
- Elkhart General Hospital, Elkhart, Indiana, 46515
- Fort Wayne Medical Oncology and Hematology Inc-Parkview, Fort Wayne, Indiana, 46845
- Reid Hospital and Health Care Services, Richmond, Indiana, 47374
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Ohio
- Wayne Hospital, Greenville, Ohio, 45331
- Oncology Hematology Care Inc-Mercy West, Cincinnati, Ohio, 45211
- Oncology Hematology Care Inc-Healthplex, Fairfield, Ohio, 45014
- University of Cincinnati, Cincinnati, Ohio, 45267
- Oncology and Hematology Care Inc-Taft, Cincinnati, Ohio, 45219
- Oncology Hematology Care Inc - Kenwood, Cincinnati, Ohio, 45236
- Oncology Hematology Care Inc - Anderson, Cincinnati, Ohio, 45230
- Oncology Hematology Care Inc-Blue Ash, Cincinnati, Ohio, 45242
- Samaritan North Health Center, Dayton, Ohio, 45415
- Good Samaritan Hospital - Dayton, Dayton, Ohio, 45406
- Grandview Hospital, Dayton, Ohio, 45405
- Upper Valley Medical Center, Troy, Ohio, 45373
- Miami Valley Hospital, Dayton, Ohio, 45409
- Kettering Medical Center, Kettering, Ohio, 45429
- Fulton County Health Center, Wauseon, Ohio, 43567
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Kentucky
- Oncology Hematology Care Inc-Crestview, Crestview Hills, Kentucky, 41017
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