Combination Chemotherapy Plus Cetuximab in Treating Patients With Liver Metastases From Colorectal Cancer
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining chemotherapy with cetuximab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with cetuximab works in treating patients with unresectable liver metastases from colorectal cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES:
-
Determine the surgical resectability rate of patients with unresectable hepatic metastases secondary to metastatic colorectal adenocarcinoma treated with oxaliplatin, fluorouracil, leucovorin calcium, and cetuximab.
-
Determine the response rate and overall survival of patients treated with this regimen.
-
Determine the quality of life of patients treated with this regimen.
-
Determine the toxicity of this regimen in these patients.
OUTLINE: This is a multicenter study.
Patients receive cetuximab IV over 1 hour (over 2 hours on day 1 of course 1 only) on days 1 and 8. Patients also receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously on days 1-2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity, for a minimum of 12 courses or until deemed to have resectable disease.
Quality of life is assessed at baseline and prior to each treatment course.
Patients are followed every 3 months for 1 year and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 67-73 patients will be accrued for this study within 4 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: cetuximab + oxaliplatin + leucovorin + fluorouracil Patients receive cetuximab IV over 1 hour (over 2 hours on day 1 of course 1 only) on days 1 and 8. Patients also receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously on days 1-2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity, for a minimum of 12 courses or until deemed to have resectable disease. Quality of life is assessed at baseline and prior to each treatment course. Patients are followed every 3 months for 1 year and then every 6 months for 3 years. |
Biological: cetuximab
Drug: fluorouracil
Drug: leucovorin calcium
Drug: oxaliplatin
|
Outcome Measures
Primary Outcome Measures
- Surgical resectability rate as assessed by surgical resection of liver metastases [Up to 4 years]
Secondary Outcome Measures
- Response rate as measured by RECIST criteria every 6 weeks [Up to 4 years]
- Overall survival [Up to 4 years]
- Quality of life as assessed by UNISCALE and Symptom Distress Scale every 6 weeks [Up to 4 years]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
History of completely resected primary adenocarcinoma of the colon or rectum
-
No gross or microscopic evidence of residual disease
-
Liver metastases, meeting 1 of the following criteria:
-
Not optimally resectable
-
Requires resection of all 3 major hepatic veins, the portal vein bifurcation, or the retrohepatic vena cava
-
Includes the main right or main left portal vein and the main hepatic vein of the opposite lobe
-
Requires more than a right or left trisegmentectomy
-
At least 6 metastatic lesions distributed diffusely in both lobes of the liver
-
Measurable disease
-
At least 1 measurable lesion ≥ 20 mm
-
No evidence of extrahepatic metastases by physical examination or x-ray
-
No previously resected extrahepatic metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- Not specified
Hematopoietic
-
Hemoglobin ≥ 9 g/dL
-
Absolute neutrophil count ≥ 1,500/mm^3
-
Platelet count ≥ 100,000/mm^3
Hepatic
-
AST ≤ 3 times upper limit of normal (ULN)
-
Bilirubin ≤ ULN
-
No preexisting chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis) that would preclude surgical resection of metastases
Renal
- Creatinine ≤ 1.5 times ULN
Cardiovascular
-
No myocardial infarction within the past 6 months
-
No clinical evidence of congestive heart failure
-
No New York Heart Association class III-IV heart disease
-
No significant cardiac disease
-
No uncontrolled hypertension
-
No unstable angina
-
No congestive heart failure
-
No uncontrolled arrhythmias
Gastrointestinal
-
Adequate oral nutrition with estimated caloric intake of ≥ 1,500 calories/day
-
No severe anorexia or frequent nausea and/or vomiting
-
No history of gastrointestinal bleeding that has not been appropriately addressed
Other
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
Able to tolerate major surgery
-
No prior allergic reaction or known sensitivity to chimerized or murine monoclonal antibody therapy
-
No documented presence of human anti-mouse antibodies
-
No known allergy to other platinum compounds
-
No other malignancy within the past 5 years except basal cell or squamous cell skin cancer, carcinoma in situ, or tumors associated with less than 10% probability of death within 5 years of diagnosis
-
No preexisting neuropathy ≥ grade 2
-
No symptomatic pulmonary fibrosis or interstitial pneumonitis
-
No uncontrolled bacterial or viral infection
-
HIV negative
-
No fungal infection
PRIOR CONCURRENT THERAPY:
Biologic therapy
-
No colony-stimulating factors within 24 hours of day 1 of each course
-
No concurrent immunotherapy
Chemotherapy
-
At least 1 year since prior adjuvant systemic fluorouracil with or without levamisole or with or without leucovorin calcium
-
No prior oxaliplatin
-
No prior systemic chemotherapy for metastatic disease
-
No prior chemoembolization for metastatic disease
-
No prior hepatic artery infusion chemotherapy for metastatic disease
-
No other concurrent chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
-
At least 12 months since prior adjuvant radiotherapy
-
Prior radiofrequency ablation allowed
-
No prior radiotherapy to the liver
-
No prior radiotherapy to more than 25% of the bone marrow
-
No concurrent radiotherapy
Surgery
-
See Disease Characteristics
-
More than 21 days since prior abdominal exploration (with or without intestinal resection)
Other
-
No prior anti-EGFR-directed therapy
-
Prior cryotherapy allowed
-
No oral cryotherapy on day 1 of each course
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mobile Infirmary Medical Center | Mobile | Alabama | United States | 36652-2144 |
| 2 | Mayo Clinic Scottsdale | Scottsdale | Arizona | United States | 85259-5499 |
| 3 | Mayo Clinic - Jacksonville | Jacksonville | Florida | United States | 32224 |
| 4 | Rush-Copley Cancer Care Center | Aurora | Illinois | United States | 60507 |
| 5 | St. Joseph Medical Center | Bloomington | Illinois | United States | 61701 |
| 6 | Graham Hospital | Canton | Illinois | United States | 61520 |
| 7 | Memorial Hospital | Carthage | Illinois | United States | 62321 |
| 8 | Eureka Community Hospital | Eureka | Illinois | United States | 61530 |
| 9 | Galesburg Clinic, PC | Galesburg | Illinois | United States | 61401 |
| 10 | Galesburg Cottage Hospital | Galesburg | Illinois | United States | 61401 |
| 11 | Mason District Hospital | Havana | Illinois | United States | 62644 |
| 12 | Hopedale Medical Complex | Hopedale | Illinois | United States | 61747 |
| 13 | Joliet Oncology-Hematology Associates, Limited - West | Joliet | Illinois | United States | 60435 |
| 14 | Kewanee Hospital | Kewanee | Illinois | United States | 61443 |
| 15 | McDonough District Hospital | Macomb | Illinois | United States | 61455 |
| 16 | Trinity Medical Center - East | Moline | Illinois | United States | 61265 |
| 17 | Moline | Illinois | United States | 61265 | |
| 18 | BroMenn Regional Medical Center | Normal | Illinois | United States | 61761 |
| 19 | Community Cancer Center | Normal | Illinois | United States | 61761 |
| 20 | Community Hospital of Ottawa | Ottawa | Illinois | United States | 61350 |
| 21 | Oncology Hematology Associates of Central Illinois, PC - Ottawa | Ottawa | Illinois | United States | 61350 |
| 22 | Cancer Treatment Center at Pekin Hospital | Pekin | Illinois | United States | 61554 |
| 23 | Proctor Hospital | Peoria | Illinois | United States | 61614 |
| 24 | CCOP - Illinois Oncology Research Association | Peoria | Illinois | United States | 61615 |
| 25 | Oncology Hematology Associates of Central Illinois, PC - Peoria | Peoria | Illinois | United States | 61615 |
| 26 | Methodist Medical Center of Illinois | Peoria | Illinois | United States | 61636 |
| 27 | OSF St. Francis Medical Center | Peoria | Illinois | United States | 61637 |
| 28 | Illinois Valley Community Hospital | Peru | Illinois | United States | 61354 |
| 29 | Perry Memorial Hospital | Princeton | Illinois | United States | 61356 |
| 30 | St. Margaret's Hospital | Spring Valley | Illinois | United States | 61362 |
| 31 | Carle Cancer Center at Carle Foundation Hospital | Urbana | Illinois | United States | 61801 |
| 32 | CCOP - Carle Cancer Center | Urbana | Illinois | United States | 61801 |
| 33 | St. Francis Hospital and Health Centers - Beech Grove Campus | Beech Grove | Indiana | United States | 46107 |
| 34 | Saint Anthony Memorial Health Centers | Michigan City | Indiana | United States | 46360 |
| 35 | Reid Hospital & Health Care Services, Incorporated | Richmond | Indiana | United States | 47374 |
| 36 | McFarland Clinic, PC | Ames | Iowa | United States | 50010 |
| 37 | Bettendorf | Iowa | United States | 52722 | |
| 38 | Cedar Rapids Oncology Associates | Cedar Rapids | Iowa | United States | 52403 |
| 39 | Mercy Capitol Hospital | Des Moines | Iowa | United States | 50307 |
| 40 | CCOP - Iowa Oncology Research Association | Des Moines | Iowa | United States | 50309 |
| 41 | John Stoddard Cancer Center at Iowa Methodist Medical Center | Des Moines | Iowa | United States | 50309 |
| 42 | Medical Oncology and Hematology Associates at John Stoddard Cancer Center | Des Moines | Iowa | United States | 50309 |
| 43 | Medical Oncology and Hematology Associates at Mercy Cancer Center | Des Moines | Iowa | United States | 50314 |
| 44 | Mercy Cancer Center at Mercy Medical Center - Des Moines | Des Moines | Iowa | United States | 50314 |
| 45 | John Stoddard Cancer Center at Iowa Lutheran Hospital | Des Moines | Iowa | United States | 50316 |
| 46 | Mercy Cancer Center at Mercy Medical Center - North Iowa | Mason City | Iowa | United States | 50401 |
| 47 | Siouxland Hematology-Oncology Associates, LLP | Sioux City | Iowa | United States | 51101 |
| 48 | Mercy Medical Center - Sioux City | Sioux City | Iowa | United States | 51104 |
| 49 | St. Luke's Regional Medical Center | Sioux City | Iowa | United States | 51104 |
| 50 | Cancer Center of Kansas, PA - Chanute | Chanute | Kansas | United States | 66720 |
| 51 | Cancer Center of Kansas, PA - Dodge City | Dodge City | Kansas | United States | 67801 |
| 52 | Cancer Center of Kansas, PA - El Dorado | El Dorado | Kansas | United States | 67042 |
| 53 | Cancer Center of Kansas, PA - Kingman | Kingman | Kansas | United States | 67068 |
| 54 | Southwest Medical Center | Liberal | Kansas | United States | 67901 |
| 55 | Cancer Center of Kansas, PA - Newton | Newton | Kansas | United States | 67114 |
| 56 | Cancer Center of Kansas, PA - Parsons | Parsons | Kansas | United States | 67357 |
| 57 | Cancer Center of Kansas, PA - Pratt | Pratt | Kansas | United States | 67124 |
| 58 | Cancer Center of Kansas, PA - Salina | Salina | Kansas | United States | 67042 |
| 59 | Cancer Center of Kansas, PA - Wellington | Wellington | Kansas | United States | 67152 |
| 60 | Associates in Womens Health, PA - North Review | Wichita | Kansas | United States | 67203 |
| 61 | Cancer Center of Kansas, PA - Medical Arts Tower | Wichita | Kansas | United States | 67208 |
| 62 | Cancer Center of Kansas, PA - Wichita | Wichita | Kansas | United States | 67214 |
| 63 | CCOP - Wichita | Wichita | Kansas | United States | 67214 |
| 64 | Via Christi Cancer Center at Via Christi Regional Medical Center | Wichita | Kansas | United States | 67214 |
| 65 | Cancer Center of Kansas, PA - Winfield | Winfield | Kansas | United States | 67156 |
| 66 | Hickman Cancer Center at Bixby Medical Center | Adrian | Michigan | United States | 49221 |
| 67 | Green Bay Oncology, Limited - Escanaba | Escanaba | Michigan | United States | 49431 |
| 68 | Dickinson County Healthcare System | Iron Mountain | Michigan | United States | 49801 |
| 69 | Haematology-Oncology Associates of Ohio and Michigan, PC | Lambertville | Michigan | United States | 48144 |
| 70 | Community Cancer Center of Monroe | Monroe | Michigan | United States | 48162 |
| 71 | Mercy Memorial Hospital - Monroe | Monroe | Michigan | United States | 48162 |
| 72 | Alexandria | Minnesota | United States | 56308 | |
| 73 | MeritCare Bemidji | Bemidji | Minnesota | United States | 56601 |
| 74 | Fairview Ridges Hospital | Burnsville | Minnesota | United States | 55337 |
| 75 | Mercy and Unity Cancer Center at Mercy Hospital | Coon Rapids | Minnesota | United States | 55433 |
| 76 | Duluth Clinic Cancer Center - Duluth | Duluth | Minnesota | United States | 55805-1983 |
| 77 | CCOP - Duluth | Duluth | Minnesota | United States | 55805 |
| 78 | Miller - Dwan Medical Center | Duluth | Minnesota | United States | 55805 |
| 79 | Fairview Southdale Hospital | Edina | Minnesota | United States | 55435 |
| 80 | Fergus Falls | Minnesota | United States | 56537 | |
| 81 | Mercy and Unity Cancer Center at Unity Hospital | Fridley | Minnesota | United States | 55432 |
| 82 | Hutchinson Area Health Care | Hutchinson | Minnesota | United States | 55350 |
| 83 | Meeker County Memorial Hospital | Lichfield | Minnesota | United States | 55355 |
| 84 | HealthEast Cancer Care at St. John's Hospital | Maplewood | Minnesota | United States | 55109 |
| 85 | Minnesota Oncology Hematology, PA - Maplewood | Maplewood | Minnesota | United States | 55109 |
| 86 | Virginia Piper Cancer Institute at Abbott - Northwestern Hospital | Minneapolis | Minnesota | United States | 55407 |
| 87 | Hennepin County Medical Center - Minneapolis | Minneapolis | Minnesota | United States | 55415 |
| 88 | Chippewa County - Montevideo Hospital and Medical Center | Montevideo | Minnesota | United States | 56265 |
| 89 | Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center | Robbinsdale | Minnesota | United States | 55422-2900 |
| 90 | Mayo Clinic Cancer Center | Rochester | Minnesota | United States | 55905 |
| 91 | Coborn Cancer Center | Saint Cloud | Minnesota | United States | 56303 |
| 92 | CCOP - Metro-Minnesota | Saint Louis Park | Minnesota | United States | 55416 |
| 93 | St. Francis Cancer Center at St. Francis Medical Center | Shakopee | Minnesota | United States | 55379 |
| 94 | HealthEast Cancer Care at St. Joseph's Hospital | St Paul | Minnesota | United States | 55102 |
| 95 | CentraCare Clinic - River Campus | St. Cloud | Minnesota | United States | 56303 |
| 96 | Park Nicollet Cancer Center | St. Louis Park | Minnesota | United States | 55416 |
| 97 | Regions Hospital Cancer Care Center | St. Paul | Minnesota | United States | 55101 |
| 98 | United Hospital | St. Paul | Minnesota | United States | 55102 |
| 99 | Ridgeview Medical Center | Waconia | Minnesota | United States | 55387 |
| 100 | HealthEast Cancer Care at Woodwinds Health Campus | Woodbury | Minnesota | United States | 55125 |
| 101 | Minnesota Oncology Hematology, PA - Woodbury | Woodbury | Minnesota | United States | 55125 |
| 102 | Big Sky Oncology | Great Falls | Montana | United States | 59405-5309 |
| 103 | CCOP - Missouri Valley Cancer Consortium | Omaha | Nebraska | United States | 68106 |
| 104 | Immanuel Medical Center | Omaha | Nebraska | United States | 68122 |
| 105 | Alegant Health Cancer Center at Bergan Mercy Medical Center | Omaha | Nebraska | United States | 68124 |
| 106 | Creighton University Medical Center | Omaha | Nebraska | United States | 68131-2197 |
| 107 | Rutherford Hospital | Rutherfordton | North Carolina | United States | 28139 |
| 108 | Bismarck Cancer Center | Bismarck | North Dakota | United States | 58501 |
| 109 | Medcenter One Hospital Cancer Care Center | Bismarck | North Dakota | United States | 58501 |
| 110 | Mid Dakota Clinic, PC | Bismarck | North Dakota | United States | 58501 |
| 111 | St. Alexius Medical Center Cancer Center | Bismarck | North Dakota | United States | 58502 |
| 112 | CCOP - MeritCare Hospital | Fargo | North Dakota | United States | 58122 |
| 113 | MeritCare Broadway | Fargo | North Dakota | United States | 58122 |
| 114 | Altru Cancer Center at Altru Hospital | Grand Forks | North Dakota | United States | 58201 |
| 115 | Wood County Oncology Center | Bowling Green | Ohio | United States | 43402 |
| 116 | Grandview Hospital | Dayton | Ohio | United States | 45405 |
| 117 | Good Samaritan Hospital | Dayton | Ohio | United States | 45406 |
| 118 | David L. Rike Cancer Center at Miami Valley Hospital | Dayton | Ohio | United States | 45409 |
| 119 | Samaritan North Cancer Care Center | Dayton | Ohio | United States | 45415 |
| 120 | Veterans Affairs Medical Center - Dayton | Dayton | Ohio | United States | 45428 |
| 121 | CCOP - Dayton | Dayton | Ohio | United States | 45429 |
| 122 | Blanchard Valley Medical Associates | Findlay | Ohio | United States | 45840 |
| 123 | Fremont Memorial Hospital | Fremont | Ohio | United States | 43420 |
| 124 | Charles F. Kettering Memorial Hospital | Kettering | Ohio | United States | 45429 |
| 125 | Lima Memorial Hospital | Lima | Ohio | United States | 45804 |
| 126 | Northwest Ohio Oncology Center | Maumee | Ohio | United States | 43537 |
| 127 | St. Luke's Hospital | Maumee | Ohio | United States | 43537 |
| 128 | Middletown Regional Hospital | Middletown | Ohio | United States | 45044 |
| 129 | St. Charles Mercy Hospital | Oregon | Ohio | United States | 43616 |
| 130 | Toledo Clinic - Oregon | Oregon | Ohio | United States | 43616 |
| 131 | Firelands Regional Medical Center | Sandusky | Ohio | United States | 44870 |
| 132 | North Coast Cancer Care, Incorporated | Sandusky | Ohio | United States | 44870 |
| 133 | Flower Hospital Cancer Center | Sylvania | Ohio | United States | 43560 |
| 134 | Mercy Hospital of Tiffin | Tiffin | Ohio | United States | 44883 |
| 135 | Toledo Hospital | Toledo | Ohio | United States | 43606 |
| 136 | St. Vincent Mercy Medical Center | Toledo | Ohio | United States | 43608 |
| 137 | Medical University of Ohio Cancer Center | Toledo | Ohio | United States | 43614 |
| 138 | CCOP - Toledo Community Hospital | Toledo | Ohio | United States | 43617 |
| 139 | Toledo Clinic, Incorporated - Main Clinic | Toledo | Ohio | United States | 43623 |
| 140 | UVMC Cancer Care Center at Upper Valley Medical Center | Troy | Ohio | United States | 45373-1300 |
| 141 | Fulton County Health Center | Wauseon | Ohio | United States | 43567 |
| 142 | Ruth G. McMillan Cancer Center at Greene Memorial Hospital | Xenia | Ohio | United States | 45385 |
| 143 | Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest | Allentown | Pennsylvania | United States | 18105 |
| 144 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822-0001 |
| 145 | Allegheny Cancer Center at Allegheny General Hospital | Pittsburgh | Pennsylvania | United States | 15212 |
| 146 | Guthrie Cancer Center at Guthrie Clinic Sayre | Sayre | Pennsylvania | United States | 18840 |
| 147 | Geisinger Medical Group - Scenery Park | State College | Pennsylvania | United States | 16801 |
| 148 | Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center | Wilkes-Barre | Pennsylvania | United States | 18711 |
| 149 | AnMed Cancer Center | Anderson | South Carolina | United States | 29621 |
| 150 | CCOP - Upstate Carolina | Spartanburg | South Carolina | United States | 29303 |
| 151 | Gibbs Regional Cancer Center at Spartanburg Regional Medical Center | Spartanburg | South Carolina | United States | 29303 |
| 152 | Avera Cancer Institute | Sioux Falls | South Dakota | United States | 57105 |
| 153 | Medical X-Ray Center, PC | Sioux Falls | South Dakota | United States | 57105 |
| 154 | Sanford Cancer Center at Sanford USD Medical Center | Sioux Falls | South Dakota | United States | 57117-5039 |
| 155 | Fredericksburg Oncology, Incorporated | Fredericksburg | Virginia | United States | 22401 |
| 156 | Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center | Green Bay | Wisconsin | United States | 54301-3526 |
| 157 | Green Bay Oncology, Limited at St. Mary's Hospital | Green Bay | Wisconsin | United States | 54303 |
| 158 | St. Mary's Hospital Medical Center - Green Bay | Green Bay | Wisconsin | United States | 54303 |
| 159 | St. Vincent Hospital Regional Cancer Center | Green Bay | Wisconsin | United States | 54307-3508 |
| 160 | Bay Area Cancer Care Center at Bay Area Medical Center | Marinette | Wisconsin | United States | 54143 |
| 161 | Green Bay Oncology, Limited - Oconto Falls | Oconto Falls | Wisconsin | United States | 54154 |
| 162 | Green Bay Oncology, Limited - Sturgeon Bay | Sturgeon Bay | Wisconsin | United States | 54235 |
Sponsors and Collaborators
- Alliance for Clinical Trials in Oncology
- National Cancer Institute (NCI)
Investigators
- Study Chair: Steven R. Alberts, MD, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCCTG-N014A
- NCI-2012-02521
- CDR0000271923