Clinical trial NCT00056030: Combination Chemotherapy Plus Cetuximab in Treating Patients With Liver Metastases From Colorectal Cancer
Official title: A Phase II Study Of Oxaliplatin (OXAL), 5-Fluorouracil (5-FU), Leucovorin (CF), and Cetuximab (C225) For Patients With Unresectable Hepatic Metastases From Metastatic Adenocarcinoma Of The Colon Or Rectum
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Metastatic Cancer
Keywords: liver metastases
stage IV colon cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-03-07
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Surgical resectability rate as assessed by surgical resection of liver metastases
timeFrame: Up to 4 years
Secondary outcomes:
measure: Response rate as measured by RECIST criteria every 6 weeks
timeFrame: Up to 4 years
measure: Overall survival
timeFrame: Up to 4 years
measure: Quality of life as assessed by UNISCALE and Symptom Distress Scale every 6 weeks
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Aurora
country: United States
facility: Rush-Copley Cancer Care Center
state: Illinois
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic, PC
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Moline
country: United States
facility: Trinity Medical Center - East
state: Illinois
city: Moline
country: United States
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center at Carle Foundation Hospital
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Centers
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services, Incorporated
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Bettendorf
country: United States
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol Hospital
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at John Stoddard Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates at Mercy Cancer Center
state: Iowa
city: Des Moines
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: John Stoddard Cancer Center at Iowa Lutheran Hospital
state: Iowa
city: Mason City
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - North Iowa
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Adrian
country: United States
facility: Hickman Cancer Center at Bixby Medical Center
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology, Limited - Escanaba
state: Michigan
city: Iron Mountain
country: United States
facility: Dickinson County Healthcare System
state: Michigan
city: Lambertville
country: United States
facility: Haematology-Oncology Associates of Ohio and Michigan, PC
state: Michigan
city: Monroe
country: United States
facility: Community Cancer Center of Monroe
state: Michigan
city: Monroe
country: United States
facility: Mercy Memorial Hospital - Monroe
state: Michigan
city: Alexandria
country: United States
state: Minnesota
city: Bemidji
country: United States
facility: MeritCare Bemidji
state: Minnesota
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Duluth
country: United States
facility: Duluth Clinic Cancer Center - Duluth
state: Minnesota
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Duluth
country: United States
facility: Miller - Dwan Medical Center
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fergus Falls
country: United States
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Lichfield
country: United States
facility: Meeker County Memorial Hospital
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Montevideo
country: United States
facility: Chippewa County - Montevideo Hospital and Medical Center
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: St Paul
country: United States
facility: HealthEast Cancer Care at St. Joseph's Hospital
state: Minnesota
city: St. Cloud
country: United States
facility: CentraCare Clinic - River Campus
state: Minnesota
city: St. Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: St. Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: St. Paul
country: United States
facility: United Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: HealthEast Cancer Care at Woodwinds Health Campus
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, PA - Woodbury
state: Minnesota
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Immanuel Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Alegant Health Cancer Center at Bergan Mercy Medical Center
state: Nebraska
city: Omaha
country: United States
facility: Creighton University Medical Center
state: Nebraska
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Bismarck
country: United States
facility: Medcenter One Hospital Cancer Care Center
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic, PC
state: North Dakota
city: Bismarck
country: United States
facility: St. Alexius Medical Center Cancer Center
state: North Dakota
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Fargo
country: United States
facility: MeritCare Broadway
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Cancer Center at Altru Hospital
state: North Dakota
city: Bowling Green
country: United States
facility: Wood County Oncology Center
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: Veterans Affairs Medical Center - Dayton
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Fremont
country: United States
facility: Fremont Memorial Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Northwest Ohio Oncology Center
state: Ohio
city: Maumee
country: United States
facility: St. Luke's Hospital
state: Ohio
city: Middletown
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Oregon
country: United States
facility: St. Charles Mercy Hospital
state: Ohio
city: Oregon
country: United States
facility: Toledo Clinic - Oregon
state: Ohio
city: Sandusky
country: United States
facility: Firelands Regional Medical Center
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care, Incorporated
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Tiffin
country: United States
facility: Mercy Hospital of Tiffin
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: St. Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio Cancer Center
state: Ohio
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic, Incorporated - Main Clinic
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Wauseon
country: United States
facility: Fulton County Health Center
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Cancer Center at Allegheny General Hospital
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Cancer Center at Guthrie Clinic Sayre
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group - Scenery Park
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Cancer Center
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Fredericksburg
country: United States
facility: Fredericksburg Oncology, Incorporated
state: Virginia
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Limited at St. Mary's Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: St. Mary's Hospital Medical Center - Green Bay
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Marinette
country: United States
facility: Bay Area Cancer Care Center at Bay Area Medical Center
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Limited - Oconto Falls
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Limited - Sturgeon Bay
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Steven R. Alberts, MD
role: STUDY_CHAIR
References: