Combination Chemotherapy Plus Cetuximab in Treating Patients With Liver Metastases From Colorectal Cancer

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00056030
• Other study ID #: NCCTG-N014A
• Secondary ID: NCI-2012-02521CD
• Status: Completed
• Phase: Phase 2
• First received: March 6, 2003
• Last updated: January 20, 2017
• Start date: December 2004

Study information

• Verified date: January 2017
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Colorectal Cancer
• Colorectal Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis

Intervention

Biological:
• cetuximab

Drug:
• fluorouracil

• leucovorin calcium

• oxaliplatin

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Surgical resectability rate as assessed by surgical resection of liver metastases		Up to 4 years
Secondary	Response rate as measured by RECIST criteria every 6 weeks		Up to 4 years
Secondary	Overall survival		Up to 4 years
Secondary	Quality of life as assessed by UNISCALE and Symptom Distress Scale every 6 weeks		Up to 4 years