Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00098787
First received: December 8, 2004
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, irinotecan, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Giving bevacizumab together with combination chemotherapy may be a better way to block tumor growth. Studying the amount of an enzyme found in the tumor may help doctors plan the best treatment.

PURPOSE: This randomized phase II trial is studying giving bevacizumab, oxaliplatin, and irinotecan or giving bevacizumab, oxaliplatin, leucovorin, and fluorouracil in treating patients with metastatic or recurrent colorectal cancer.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: Oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Treatment Selection Based Upon Tumor Thymidylate Synthase Expression in Previously Untreated Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Objective Response Rate [ Time Frame: Assessed every 3 months if the patient is within 2 years of registration and every 6 months up to 4 years post-registration. ] [ Designated as safety issue: No ]
    Objective response rate is defined as proportion of patients who achieve complete response (CR) or partial response (PR). Response was assessed using Solid Tumor Response Criteria (RECIST). CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter.


Secondary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Assessed every 3 months if the patient is within 2 years of registration and every 6 months once the patient is 2-4 years post-registration. ] [ Designated as safety issue: No ]
    Progression-free survival is defined as time from randomization (to Arm A or Arm B) or registration (to Arm C) to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.

  • Overall Survival (OS) [ Time Frame: Assessed every 3 months if the patient is within 2 years of registration and every 6 months once the patient is 2-4 years post-registration. ] [ Designated as safety issue: No ]
    Overall survival is defined as time from randomization (to Arm A or Arm B) or registration (to Arm C) to death. Patients alive at last follow-up were censored.


Enrollment: 247
Study Start Date: July 2005
Estimated Study Completion Date: April 2016
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (High TS, IROX/bev)
Patients with high TS who are randomized to Arm A receive irinotecan and oxaliplatin plus bevacizumab (IROX/bev). The combination regimen is administered by giving bevacizumab IV over 30-90 minutes followed by oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on days 1 and 15 every 28 days until disease progression or until any criterion specified in protocol is met.
Biological: bevacizumab
Given IV
Other Name: NSC 704865, RhuMAb VEGF, Recombinant Humanized Monoclonal Anti-VEGF Antibody
Drug: irinotecan hydrochloride
Given IV
Other Name: Camptothecin-11, CPT-11, Camptosar
Drug: Oxaliplatin
Given IV
Other Name: Eloxatin, trans-l-diaminocyclohexane oxalatoplatinum, cis-[oxalato(trans-l-1,2-diaminocyclohexane)platinum(II)].
Experimental: Arm B (High TS, FOLFOX/bev)
Patients with high TS who are randomized to Arm B receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev). The combination regimen is administered by giving bevacizumab and oxaliplatin as in Arm A, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15 every 28 days until disease progression or until any criterion specified in protocol is met.
Biological: bevacizumab
Given IV
Other Name: NSC 704865, RhuMAb VEGF, Recombinant Humanized Monoclonal Anti-VEGF Antibody
Drug: fluorouracil
Given IV
Other Name: 5-Fluorouracil, 5-FU, Adrucil, Efudex
Drug: leucovorin calcium
Given IV
Other Name: Leucovorin, Wellcovorin' citrovorum factor, folinic acid, 5-formyl tetrahydrofolate, LV, LCV.
Drug: Oxaliplatin
Given IV
Other Name: Eloxatin, trans-l-diaminocyclohexane oxalatoplatinum, cis-[oxalato(trans-l-1,2-diaminocyclohexane)platinum(II)].
Experimental: Arm C (Low or intermediate TS, FOLFOX/bev)
Patients with low or intermediate TS receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev) as in Arm B.
Biological: bevacizumab
Given IV
Other Name: NSC 704865, RhuMAb VEGF, Recombinant Humanized Monoclonal Anti-VEGF Antibody
Drug: fluorouracil
Given IV
Other Name: 5-Fluorouracil, 5-FU, Adrucil, Efudex
Drug: leucovorin calcium
Given IV
Other Name: Leucovorin, Wellcovorin' citrovorum factor, folinic acid, 5-formyl tetrahydrofolate, LV, LCV.
Drug: Oxaliplatin
Given IV
Other Name: Eloxatin, trans-l-diaminocyclohexane oxalatoplatinum, cis-[oxalato(trans-l-1,2-diaminocyclohexane)platinum(II)].

Detailed Description:

OBJECTIVES:

  • Compare the response rate (complete and partial), progression-free survival, and overall survival of patients with previously untreated metastatic or locally recurrent colorectal adenocarcinoma with high vs low thymidylate synthase (TS) expression treated with fluorouracil, leucovorin calcium, oxaliplatin, and bevacizumab or irinotecan, oxaliplatin, and bevacizumab.
  • Compare the toxicity of these regimens in these patients.
  • Correlate gene expression with response rates in patients treated with these regimens.
  • Correlate gene expression with toxicity of these regimens in these patients.
  • Correlate dihydropyrimidine dehydrogenase, thymidine phosphorylase, and mammalian excision repair cross complementary protein expression with antitumor response in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to thymidylate synthase (TS) expression levels (high vs low or indeterminate). Patients with high TS expression are randomized to 1 of 2 treatment arms (Arms A or B). Patients with low or indeterminate TS expression are assigned to Arm C.

  • Arm A: Patients receive bevacizumab IV over 30-90 minutes followed by oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on days 1 and 15.
  • Arm B: Patients receive bevacizumab and oxaliplatin as in arm A, leucovorin calcium IV over 2 hours, and fluorouracil IV over 5 minutes and then continuously over 46 hours on days 1 and 15.
  • Arm C: Patients receive bevacizumab, oxaliplatin, leucovorin calcium, and fluorouracil as in arm B.

In all arms, courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Patients are followed up every 3 months for 2 years and then every 6 months for 2 years from the date of study registration.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION:

  • Metastatic or locally recurrent colorectal adenocarcinoma
  • Measurable disease
  • At least 2 formalin-fixed paraffin embedded core needle biopsies OR fine needle aspirate containing a minimum of 3 clusters of malignant cells and fixed tissue from the previous biopsy
  • If no tissue samples are available the patient must be willing to undergo biopsy of a metastatic site
  • Age 18 and over
  • Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 unless patient is receiving full-dose anticoagulants AND the following criteria are met:

    • In-range INR (usually between 2 and 3) AND on a stable dose of warfarin or low molecular weight heparin
    • No active bleeding or pathological condition that is associated with a high risk of bleeding
  • Partial thromboplastin time (PTT) < 1.5 times upper limit of normal (ULN)
  • Alanine transaminase (ALT) and aspartate aminotransferase (AST) < 3 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • Creatinine ≤ 1.8 mg/dL
  • Meets 1 of the following criteria:

    • Protein negative on urine dipstick
    • Urine protein/creatinine ratio < 1.0
    • Less than 2 g protein on 24-hour urine collection
  • Patients with a history of hypertension must meet the following criteria:

    • Blood pressure < 150/90 mm Hg
    • Stable regimen of anti-hypertensive therapy
  • More than 28 days since prior major or open surgery
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study participation
  • Prior non-colorectal malignancies are allowed provided the following criteria are met:

    • No current clinical evidence of persistent or recurrent disease
    • No active therapy for non-colorectal malignancy, including hormonal therapy

EXCLUSION:

  • Pregnant or nursing
  • Arterial thromboembolic events within the past 6 months, including the following:

    • Transient ischemic attack
    • Cerebrovascular accident
    • Unstable angina pectoris
    • Myocardial infarction
  • Symptomatic arrhythmia
  • Symptomatic congestive heart failure
  • Clinically significant peripheral artery disease
  • New York Heart Association class III or IV heart disease
  • Serious nonhealing wound, ulcer, or bone fracture within the past 28 days
  • Significant traumatic injury within the past 28 days
  • Neuropathy ≥ grade 2
  • Ongoing or active infection
  • Concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
  • Prior chemotherapy for metastatic disease. Adjuvant therapy completed at least 12 months before first evidence of metastasis allowed
  • Cardiovascular, renal, hepatic, or other nonmalignant systemic disease that would preclude study therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00098787

  Hide Study Locations
Locations
United States, California
California Cancer Care, Incorporated - Greenbrae
Greenbrae, California, United States, 94904
United States, Colorado
Aurora Presbyterian Hospital
Aurora, Colorado, United States, 80012
Boulder Community Hospital
Boulder, Colorado, United States, 80301-9019
Penrose Cancer Center at Penrose Hospital
Colorado Springs, Colorado, United States, 80933
St. Joseph Hospital
Denver, Colorado, United States, 80218
CCOP - Colorado Cancer Research Program
Denver, Colorado, United States, 80224-2522
Porter Adventist Hospital
Denver, Colorado, United States, 80210
Presbyterian - St. Luke's Medical Center
Denver, Colorado, United States, 80218
St. Anthony Central Hospital
Denver, Colorado, United States, 80204
Rose Medical Center
Denver, Colorado, United States, 80220
Swedish Medical Center
Englewood, Colorado, United States, 80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
Grand Junction, Colorado, United States, 81502
North Colorado Medical Center
Greeley, Colorado, United States, 80631
Littleton Adventist Hospital
Littleton, Colorado, United States, 80122
Sky Ridge Medical Center
Lone Tree, Colorado, United States, 80124
Hope Cancer Care Center at Longmont United Hospital
Longmont, Colorado, United States, 80501
McKee Medical Center
Loveland, Colorado, United States, 80539
Parker Adventist Hospital
Parker, Colorado, United States, 80138
St. Mary - Corwin Regional Medical Center
Pueblo, Colorado, United States, 81004
North Suburban Medical Center
Thornton, Colorado, United States, 80229
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, United States, 80033
United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
Veterans Affairs Medical Center - Atlanta (Decatur)
Decatur, Georgia, United States, 30033
United States, Illinois
Hematology and Oncology Associates
Chicago, Illinois, United States, 60611
Saint Joseph Hospital
Chicago, Illinois, United States, 60657
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
Provena St. Mary's Regional Cancer Center - Kankakee
Kankakee, Illinois, United States, 60901
North Shore Oncology and Hematology Associates, Limited - Libertyville
Libertyville, Illinois, United States, 60048
Cancer Care and Hematology Specialists of Chicagoland - Niles
Niles, Illinois, United States, 60714
Swedish-American Regional Cancer Center
Rockford, Illinois, United States, 61104-2315
Hematology Oncology Associates - Skokie
Skokie, Illinois, United States, 60076
United States, Indiana
Elkhart General Hospital
Elkhart, Indiana, United States, 46515
Veterans Affairs Medical Center - Indianapolis
Indianapolis, Indiana, United States, 46202
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202-5289
William N. Wishard Memorial Hospital
Indianapolis, Indiana, United States, 46202
Howard Community Hospital
Kokomo, Indiana, United States, 46904
Center for Cancer Therapy at LaPorte Hospital and Health Services
La Porte, Indiana, United States, 46350
Saint Joseph Regional Medical Center
Mishawaka, Indiana, United States, 46545-1470
Memorial Hospital of South Bend
South Bend, Indiana, United States, 46601
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
United States, Iowa
McCreery Cancer Center at Ottumwa Regional
Ottumwa, Iowa, United States, 52501
Mercy Medical Center - Sioux City
Sioux City, Iowa, United States, 51102
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, United States, 51101
St. Luke's Regional Medical Center
Sioux City, Iowa, United States, 51104
United States, Michigan
West Michigan Cancer Center
Kalamazoo, Michigan, United States, 49007-3731
Bronson Methodist Hospital
Kalamazoo, Michigan, United States, 49007
Borgess Medical Center
Kalamazoo, Michigan, United States, 49001
Lakeside Cancer Specialists, PLLC
Saint Joseph, Michigan, United States, 49085
Lakeland Regional Cancer Care Center - St. Joseph
St. Joseph, Michigan, United States, 49085
United States, Minnesota
MeritCare Bemidji
Bemidji, Minnesota, United States, 56601
Fairview Ridges Hospital
Burnsville, Minnesota, United States, 55337
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, United States, 55433
Fairview Southdale Hospital
Edina, Minnesota, United States, 55435
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, United States, 55432
Hutchinson Area Health Care
Hutchinson, Minnesota, United States, 55350
Minnesota Oncology - Maplewood
Maplewood, Minnesota, United States, 55109
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, United States, 55109
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55415
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, United States, 55407
New Ulm Medical Center
New Ulm, Minnesota, United States, 56073
Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, United States, 55422-2900
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, United States, 55416
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, United States, 55416
United Hospital
Saint Paul, Minnesota, United States, 55102
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, United States, 55379
Regions Hospital Cancer Care Center
St. Paul, Minnesota, United States, 55101
Lakeview Hospital
Stillwater, Minnesota, United States, 55082
Ridgeview Medical Center
Waconia, Minnesota, United States, 55387
Willmar Cancer Center at Rice Memorial Hospital
Willmar, Minnesota, United States, 56201
Minnesota Oncology - Woodbury
Woodbury, Minnesota, United States, 55125
United States, Nebraska
Cancer Resource Center - Lincoln
Lincoln, Nebraska, United States, 68510
Lakeside Hospital
Omaha, Nebraska, United States, 68130
Alegant Health Cancer Center at Bergan Mercy Medical Center
Omaha, Nebraska, United States, 68124
Creighton University Medical Center
Omaha, Nebraska, United States, 68131-2197
Immanuel Medical Center
Omaha, Nebraska, United States, 68122
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
United States, New Jersey
Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton
Marlton, New Jersey, United States, 08053
United States, North Dakota
Roger Maris Cancer Center at MeritCare Hospital
Fargo, North Dakota, United States, 58122
CCOP - MeritCare Hospital
Fargo, North Dakota, United States, 58122
United States, Ohio
Adena Regional Medical Center
Chillicothe, Ohio, United States, 45601
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, United States, 44109
CCOP - Columbus
Columbus, Ohio, United States, 43215
Doctors Hospital at Ohio Health
Columbus, Ohio, United States, 43228
Mount Carmel Health - West Hospital
Columbus, Ohio, United States, 43222
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, United States, 43214-3998
Grant Medical Center Cancer Care
Columbus, Ohio, United States, 43215
Grady Memorial Hospital
Delaware, Ohio, United States, 43015
Fairfield Medical Center
Lancaster, Ohio, United States, 43130
St. Rita's Medical Center
Lima, Ohio, United States, 45801
Strecker Cancer Center at Marietta Memorial Hospital
Marietta, Ohio, United States, 45750
Knox Community Hospital
Mount Vernon, Ohio, United States, 43050
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Newark, Ohio, United States, 43055
Southern Ohio Medical Center Cancer Center
Portsmouth, Ohio, United States, 45662
Community Hospital of Springfield and Clark County
Springfield, Ohio, United States, 45505
Genesis - Good Samaritan Hospital
Zanesville, Ohio, United States, 43701
United States, Oklahoma
Natalie Warren Bryant Cancer Center at St. Francis Hospital
Tulsa, Oklahoma, United States, 74136
United States, Pennsylvania
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
Allentown, Pennsylvania, United States, 18105
Bryn Mawr Hospital
Bryn Mawr, Pennsylvania, United States, 19010
Cancer Center of Paoli Memorial Hospital
Paoli, Pennsylvania, United States, 19301-1792
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
Reading, Pennsylvania, United States, 19612-6052
Lankenau Cancer Center at Lankenau Hospital
Wynnewood, Pennsylvania, United States, 19096
CCOP - Main Line Health
Wynnewood, Pennsylvania, United States, 19096
United States, South Dakota
Avera Cancer Institute
Sioux Falls, South Dakota, United States, 57105
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
United States, Tennessee
Erlanger Cancer Center at Erlanger Hospital - Baroness
Chattanooga, Tennessee, United States, 37403
United States, Texas
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
Sponsors and Collaborators
Eastern Cooperative Oncology Group
Investigators
Study Chair: Neal J. Meropol, MD Fox Chase Cancer Center
Study Chair: Jean L. Grem, MD University of Nebraska
  More Information

No publications provided

Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00098787     History of Changes
Other Study ID Numbers: CDR0000398096, E4203, U10CA021115
Study First Received: December 8, 2004
Results First Received: May 27, 2014
Last Updated: July 22, 2014
Health Authority: United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:
recurrent colon cancer
stage IV colon cancer
recurrent rectal cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Oxaliplatin
Irinotecan
Fluorouracil
Formyltetrahydrofolates
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014