Oxaliplatin and Bevacizumab (Avastin™) With Either Fluorouracil and Leucovorin or Capecitabine in Treating Patients With Advanced Colorectal Cancer

Colorectal Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00062426
• Other study ID #: CDR0000304771
• Secondary ID: PROLOGUE-SANOFI-
• Status: Completed
• Phase: Phase 3
• First received: June 5, 2003
• Last updated: November 5, 2013
• Start date: May 2003
• Est. completion date: February 2011

Study information

• Verified date: April 2004
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• bevacizumab

Drug:
• capecitabine

• fluorouracil

• leucovorin calcium

• oxaliplatin

Locations

Country	Name	City	State
United States	Advanced Oncology Associates	Armonk	New York
United States	Peachtree Hematology and Oncology Consultants, P.C.	Atlanta	Georgia
United States	Lone Star Oncology	Austin	Texas
United States	Greater Baltimore Medical Center and Cancer Center	Baltimore	Maryland
United States	Deaconess Billings Clinic Cancer Center	Billings	Montana
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Lynn Regional Cancer Center West	Boca Raton	Florida
United States	Cedar Rapids Oncology Associates	Cedar Rapids	Iowa
United States	Charleston Hematology-Oncology, P.A.	Charleston	South Carolina
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	North Idaho Cancer Center	Coeur d'Alene	Idaho
United States	Hematology Oncology Consultants Inc	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Rocky Mountain Cancer Centers - Midtown	Denver	Colorado
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	North Shore Hematology/Oncology Associates, P.C.	East Setauket	New York
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Southeastern Medical Oncology Center	Goldsboro	North Carolina
United States	Arena Oncology Associates	Great Neck	New York
United States	California Cancer Care, Inc.	Greenbrae	California
United States	Physicians East - Quadrangle	Greenville	North Carolina
United States	Jackson Oncology Associates, PLLC	Jackson	Mississippi
United States	Florida Oncology Associates	Jacksonville	Florida
United States	McCleod Cancer and Blood Center	Johnson City	Tennessee
United States	Veterans Affairs Medical Center - Kansas City	Kansas City	Missouri
United States	Valley Tumor Medical Group	Lancaster	California
United States	Memphis Cancer Center	Memphis	Tennessee
United States	West Clinic	Memphis	Tennessee
United States	Medical Consultants	Milwaukee	Wisconsin
United States	Sarah Cannon Cancer Center at Centennial Medical Center	Nashville	Tennessee
United States	New York University Medical Center	New York	New York
United States	St. Vincents Comprehensive Cancer Center	New York	New York
United States	Hematology and Oncology Consultants, P.A.	Orlando	Florida
United States	Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Pennsylvania Oncology Hematology Associates	Philadelphia	Pennsylvania
United States	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Hematology Oncology Associates of theTreasure Coast - Port St. Lucie	Port St. Lucie	Florida
United States	Raleigh Hematology/Oncology Associates, P.A. - Wake Practice	Raleigh	North Carolina
United States	Cancer and Blood Institute of the Desert	Rancho Mirage	California
United States	West Suburban Center for Cancer Care	River Forest	Illinois
United States	Saint Anthony Medical Center	Rockford	Illinois
United States	Hematology/Oncology of Salem	Salem	Oregon
United States	South Texas Oncology and Hematology	San Antonio	Texas
United States	CCOP - Northern Indiana CR Consortium	South Bend	Indiana
United States	Center for Cancer Prevention and Care at Scott and White Clinic	Temple	Texas
United States	Northwestern Connecticut Oncology-Hematology Associates	Torrington	Connecticut
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	New York Medical College	Valhalla	New York
United States	Cooper Cancer Institute at Cooper University Hospital	Voorhees	New Jersey
United States	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
United States	Palm Beach Cancer Institute	West Palm Beach	Florida
United States	CCOP - Wichita	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Prologue Research International

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation