Clinical trial NCT00062426: Oxaliplatin and Bevacizumab (Avastin™) With Either Fluorouracil and Leucovorin or Capecitabine in Treating Patients With Advanced Colorectal Cancer
Official title: A Randomized, Prospective Study Comparing Three Regimens Of Eloxatin ™ Plus Fluoropyrimidine For Evaluation Of Safety And Tolerability In First Line Treatment Of Patients With Advanced Colorectal Cancer (Tree Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the colon
adenocarcinoma of the rectum
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-06-06
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, leucovorin, and capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them in different combinations may kill more tumor cells. Monoclonal antibodies, such as bevacizumab (Avastin™), can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. It is not yet known which regimen works better in treating advanced colorectal cancer.

PURPOSE: This randomized phase III trial is to see if oxaliplatin and bevacizumab work better when combined with either fluorouracil and leucovorin or capecitabine in treating patients who have metastatic or recurrent colorectal cancer.

Detailed description: OBJECTIVES:

* Compare the incidence of grade 3 and 4 toxic effects occurring within the first 12 weeks of treatment with 2 different schedules of oxaliplatin, bevacizumab (Avastin™), leucovorin calcium, and fluorouracil or with oxaliplatin, Avastin™, and capecitabine in patients with advanced colorectal cancer.
* Compare the overall response rate, progression-free survival, and time to treatment failure in patients treated with these regimens.
* Compare the composite toxicity of these regimens in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive bevacizumab (Avastin™) IV over 30-90 minutes, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil (5-FU) IV over 46 hours beginning on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive Avastin™ IV over 30-90 minutes and oxaliplatin IV over 2 hours on days 1 and 15 and leucovorin calcium IV over 10 minutes and 5-FU IV over 3 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
* Arm III: Patients receive Avastin™ IV over 30-90 minutes and oxaliplatin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1 month, every 3 months for at least 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 375 patients (125 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed adenocarcinoma of the colon or rectum

  * Metastatic or recurrent disease not amenable to potentially curative treatment
* At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

  * Histological or cytological confirmation is required for a solitary target lesion
* No CNS metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* ECOG 0-1

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic

* Bilirubin no greater than 2 times upper limit of normal (ULN)
* SGPT and SGOT no greater than 3 times ULN

Renal

* Creatinine no greater than 1.5 times ULN
* Creatinine clearance at least 30 mL/min

Cardiovascular

* No myocardial infarction within the past 6 months
* No clinical evidence of congestive heart failure
* No unstable coronary artery disease

Pulmonary

* No interstitial pneumonia
* No extensive symptomatic fibrosis of the lungs

Gastrointestinal

* Able to tolerate oral medication
* No lack of physical integrity of the upper gastrointestinal tract
* No malabsorption syndrome
* No swallowing difficulties

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 6 months after study participation
* No other concurrent serious illness
* No uncontrolled infection
* No other concurrent malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix or any other cancer for which the patient has been off all therapy and in remission for at least 5 years
* No peripheral neuropathy
* No hypersensitivity to any of the study drugs or their ingredients
* No known dihydropyrimidine dehydrogenase deficiency
* No other medical or psychiatric disorder that would preclude giving informed consent or complying with study

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent prophylactic hematopoietic growth factor therapy
* No prior bevacizumab (Avastin™)

Chemotherapy

* At least 6 months since prior adjuvant fluorouracil, leucovorin calcium, and irinotecan
* No prior oxaliplatin
* No prior chemotherapy for metastatic or recurrent disease
* No other concurrent chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* No concurrent radiotherapy unless for the control of bone pain

Surgery

* Recovered from prior surgery
* No prior organ allografts

Other

* More than 4 weeks since prior investigational drugs
* No concurrent iced mouth rinses for the prevention of stomatitis
* No concurrent cold cap alopecia prevention
* No concurrent pyridoxine
* No concurrent sorivudine or chemically-related analogues (e.g., brivudine)
* No concurrent chronic aspirin, nonsteroidal anti-inflammatory drugs, or warfarin

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Comprehensive Cancer Center
state: Alabama
city: Tucson
country: United States
facility: Arizona Clinical Research Center
state: Arizona
city: Greenbrae
country: United States
facility: California Cancer Care, Inc.
state: California
city: Lancaster
country: United States
facility: Valley Tumor Medical Group
state: California
city: Rancho Mirage
country: United States
facility: Cancer and Blood Institute of the Desert
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers - Midtown
state: Colorado
city: Torrington
country: United States
facility: Northwestern Connecticut Oncology-Hematology Associates
state: Connecticut
city: Washington
country: United States
facility: Lombardi Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Boca Raton
country: United States
facility: Lynn Regional Cancer Center West
state: Florida
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Jacksonville
country: United States
facility: Florida Oncology Associates
state: Florida
city: Orlando
country: United States
facility: Hematology and Oncology Consultants, P.A.
state: Florida
city: Port St. Lucie
country: United States
facility: Hematology Oncology Associates of theTreasure Coast - Port St. Lucie
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Cancer Institute
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology and Oncology Consultants, P.C.
state: Georgia
city: Coeur d'Alene
country: United States
facility: North Idaho Cancer Center
state: Idaho
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Park Ridge
country: United States
facility: Lutheran General Cancer Care Center
state: Illinois
city: River Forest
country: United States
facility: West Suburban Center for Cancer Care
state: Illinois
city: Rockford
country: United States
facility: Saint Anthony Medical Center
state: Illinois
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Associates
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center and Cancer Center
state: Maryland
city: Jackson
country: United States
facility: Jackson Oncology Associates, PLLC
state: Mississippi
city: Kansas City
country: United States
facility: Veterans Affairs Medical Center - Kansas City
state: Missouri
city: Billings
country: United States
facility: Deaconess Billings Clinic Cancer Center
state: Montana
city: Voorhees
country: United States
facility: Cooper Cancer Institute at Cooper University Hospital
state: New Jersey
city: Armonk
country: United States
facility: Advanced Oncology Associates
state: New York
city: East Setauket
country: United States
facility: North Shore Hematology/Oncology Associates, P.C.
state: New York
city: Great Neck
country: United States
facility: Arena Oncology Associates
state: New York
city: New York
country: United States
facility: St. Vincents Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: New York University Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center
state: North Carolina
city: Greenville
country: United States
facility: Physicians East - Quadrangle
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Hematology/Oncology Associates, P.A. - Wake Practice
state: North Carolina
city: Columbus
country: United States
facility: Hematology Oncology Consultants Inc
state: Ohio
city: Salem
country: United States
facility: Hematology/Oncology of Salem
state: Oregon
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematology Associates
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hillman Cancer Center at University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Charleston
country: United States
facility: Charleston Hematology-Oncology, P.A.
state: South Carolina
city: Johnson City
country: United States
facility: McCleod Cancer and Blood Center
state: Tennessee
city: Memphis
country: United States
facility: Memphis Cancer Center
state: Tennessee
city: Memphis
country: United States
facility: West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Cancer Center at Centennial Medical Center
state: Tennessee
city: Austin
country: United States
facility: Lone Star Oncology
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: San Antonio
country: United States
facility: South Texas Oncology and Hematology
state: Texas
city: Temple
country: United States
facility: Center for Cancer Prevention and Care at Scott and White Clinic
state: Texas
city: Milwaukee
country: United States
facility: Medical Consultants
state: Wisconsin
Study officials:
affiliation: Prologue Research International
name: Richard A. Gams, MD
role: STUDY_CHAIR
affiliation: Sanofi-Synthelabo
name: Lauri Welles, MD
References:
citation: Leighl NB, Bennouna J, Yi J, Moore N, Hambleton J, Hurwitz H. Bleeding events in bevacizumab-treated cancer patients who received full-dose anticoagulation and remained on study. Br J Cancer. 2011 Feb 1;104(3):413-8. doi: 10.1038/sj.bjc.6606074. Epub 2011 Jan 18.