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AzTrials

Colorectal CancerPhase 2NCT00098787

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

A Phase 2 study testing bevacizumab, fluorouracil and irinotecan hydrochloride in people with Colorectal Cancer, run by Eastern Cooperative Oncology Group at 110 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
bevacizumab, fluorouracil and irinotecan hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
247 participants
Where
110 sitesUnited States
Study dates
8 Sep 2005to Apr 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 28Show fewer
  • 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

Who cannot join

  • Pregnant or nursing
  • Arterial thromboembolic events within the past 6 months, including the following:
  • Transient ischemic attack
  • Cerebrovascular accident
  • Unstable angina pectoris
  • Myocardial infarction
Show all 17Show fewer
  • 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

Trial locations and contacts

110 sites in 1 country.

110 sites in 1 country

United States110 sites

  • Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest

    Allentown, Pennsylvania, 18105

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

  • Aurora Presbyterian Hospital

    Aurora, Colorado, 80012

  • MeritCare Bemidji

    Bemidji, Minnesota, 56601

  • Boulder Community Hospital

    Boulder, Colorado, 80301-9019

  • Bryn Mawr Hospital

    Bryn Mawr, Pennsylvania, 19010

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Erlanger Cancer Center at Erlanger Hospital - Baroness

    Chattanooga, Tennessee, 37403

  • Robert H. Lurie Comprehensive Cancer Center at Northwestern University

    Chicago, Illinois, 60611-3013

  • Hematology and Oncology Associates

    Chicago, Illinois, 60611

  • Saint Joseph Hospital

    Chicago, Illinois, 60657

  • Adena Regional Medical Center

    Chillicothe, Ohio, 45601

  • Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

  • MetroHealth Cancer Care Center at MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Penrose Cancer Center at Penrose Hospital

    Colorado Springs, Colorado, 80933

  • Riverside Methodist Hospital Cancer Care

    Columbus, Ohio, 43214-3998

  • CCOP - Columbus

    Columbus, Ohio, 43215

  • Grant Medical Center Cancer Care

    Columbus, Ohio, 43215

  • Mount Carmel Health - West Hospital

    Columbus, Ohio, 43222

  • Doctors Hospital at Ohio Health

    Columbus, Ohio, 43228

  • Mercy and Unity Cancer Center at Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Veterans Affairs Medical Center - Atlanta (Decatur)

    Decatur, Georgia, 30033

  • Decatur Memorial Hospital Cancer Care Institute

    Decatur, Illinois, 62526

  • Grady Memorial Hospital

    Delaware, Ohio, 43015

  • St. Anthony Central Hospital

    Denver, Colorado, 80204

  • Porter Adventist Hospital

    Denver, Colorado, 80210

  • Presbyterian - St. Luke's Medical Center

    Denver, Colorado, 80218

  • St. Joseph Hospital

    Denver, Colorado, 80218

  • Rose Medical Center

    Denver, Colorado, 80220

  • CCOP - Colorado Cancer Research Program

    Denver, Colorado, 80224-2522

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Elkhart General Hospital

    Elkhart, Indiana, 46515

  • Swedish Medical Center

    Englewood, Colorado, 80110

  • CCOP - MeritCare Hospital

    Fargo, North Dakota, 58122

  • Roger Maris Cancer Center at MeritCare Hospital

    Fargo, North Dakota, 58122

  • Mercy and Unity Cancer Center at Unity Hospital

    Fridley, Minnesota, 55432

  • University of Florida Shands Cancer Center

    Gainesville, Florida, 32610-0232

  • St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center

    Grand Junction, Colorado, 81502

  • North Colorado Medical Center

    Greeley, Colorado, 80631

  • California Cancer Care, Incorporated - Greenbrae

    Greenbrae, California, 94904

  • Hutchinson Area Health Care

    Hutchinson, Minnesota, 55350

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202-5289

  • Veterans Affairs Medical Center - Indianapolis

    Indianapolis, Indiana, 46202

  • William N. Wishard Memorial Hospital

    Indianapolis, Indiana, 46202

  • Borgess Medical Center

    Kalamazoo, Michigan, 49001

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007-3731

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Provena St. Mary's Regional Cancer Center - Kankakee

    Kankakee, Illinois, 60901

  • Howard Community Hospital

    Kokomo, Indiana, 46904

  • Center for Cancer Therapy at LaPorte Hospital and Health Services

    La Porte, Indiana, 46350

  • Fairfield Medical Center

    Lancaster, Ohio, 43130

  • North Shore Oncology and Hematology Associates, Limited - Libertyville

    Libertyville, Illinois, 60048

  • St. Rita's Medical Center

    Lima, Ohio, 45801

  • Cancer Resource Center - Lincoln

    Lincoln, Nebraska, 68510

  • Littleton Adventist Hospital

    Littleton, Colorado, 80122

  • Sky Ridge Medical Center

    Lone Tree, Colorado, 80124

  • Hope Cancer Care Center at Longmont United Hospital

    Longmont, Colorado, 80501

  • McKee Medical Center

    Loveland, Colorado, 80539

  • HealthEast Cancer Care at St. John's Hospital

    Maplewood, Minnesota, 55109

  • Minnesota Oncology - Maplewood

    Maplewood, Minnesota, 55109

  • Strecker Cancer Center at Marietta Memorial Hospital

    Marietta, Ohio, 45750

  • Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton

    Marlton, New Jersey, 08053

  • Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center - Minneapolis

    Minneapolis, Minnesota, 55415

  • Saint Joseph Regional Medical Center

    Mishawaka, Indiana, 46545-1470

  • Knox Community Hospital

    Mount Vernon, Ohio, 43050

  • New Ulm Medical Center

    New Ulm, Minnesota, 56073

  • Licking Memorial Cancer Care Program at Licking Memorial Hospital

    Newark, Ohio, 43055

  • Cancer Care and Hematology Specialists of Chicagoland - Niles

    Niles, Illinois, 60714

  • CCOP - Missouri Valley Cancer Consortium

    Omaha, Nebraska, 68106

  • Immanuel Medical Center

    Omaha, Nebraska, 68122

  • Alegant Health Cancer Center at Bergan Mercy Medical Center

    Omaha, Nebraska, 68124

  • Lakeside Hospital

    Omaha, Nebraska, 68130

  • Creighton University Medical Center

    Omaha, Nebraska, 68131-2197

  • McCreery Cancer Center at Ottumwa Regional

    Ottumwa, Iowa, 52501

  • Cancer Center of Paoli Memorial Hospital

    Paoli, Pennsylvania, 19301-1792

  • Parker Adventist Hospital

    Parker, Colorado, 80138

  • Fox Chase Cancer Center - Philadelphia

    Philadelphia, Pennsylvania, 19111-2497

  • Southern Ohio Medical Center Cancer Center

    Portsmouth, Ohio, 45662

  • St. Mary - Corwin Regional Medical Center

    Pueblo, Colorado, 81004

  • McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center

    Reading, Pennsylvania, 19612-6052

  • Humphrey Cancer Center at North Memorial Outpatient Center

    Robbinsdale, Minnesota, 55422-2900

  • Swedish-American Regional Cancer Center

    Rockford, Illinois, 61104-2315

  • Lakeland Regional Cancer Care Center - St. Joseph

    Saint Joseph, Michigan, 49085

  • Lakeside Cancer Specialists, PLLC

    Saint Joseph, Michigan, 49085

  • CCOP - Metro-Minnesota

    Saint Louis Park, Minnesota, 55416

  • Park Nicollet Cancer Center

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital Cancer Care Center

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • St. Francis Cancer Center at St. Francis Medical Center

    Shakopee, Minnesota, 55379

  • Siouxland Hematology-Oncology Associates, LLP

    Sioux City, Iowa, 51101

  • Mercy Medical Center - Sioux City

    Sioux City, Iowa, 51102

  • St. Luke's Regional Medical Center

    Sioux City, Iowa, 51104

  • Avera Cancer Institute

    Sioux Falls, South Dakota, 57105

  • Sanford Cancer Center at Sanford USD Medical Center

    Sioux Falls, South Dakota, 57117-5039

  • Hematology Oncology Associates - Skokie

    Skokie, Illinois, 60076

  • CCOP - Northern Indiana CR Consortium

    South Bend, Indiana, 46601

  • Memorial Hospital of South Bend

    South Bend, Indiana, 46601

  • Community Hospital of Springfield and Clark County

    Springfield, Ohio, 45505

  • Lakeview Hospital

    Stillwater, Minnesota, 55082

  • CCOP - Scott and White Hospital

    Temple, Texas, 76508

  • North Suburban Medical Center

    Thornton, Colorado, 80229

  • Natalie Warren Bryant Cancer Center at St. Francis Hospital

    Tulsa, Oklahoma, 74136

  • Ridgeview Medical Center

    Waconia, Minnesota, 55387

  • Exempla Lutheran Medical Center

    Wheat Ridge, Colorado, 80033

  • Willmar Cancer Center at Rice Memorial Hospital

    Willmar, Minnesota, 56201

  • Minnesota Oncology - Woodbury

    Woodbury, Minnesota, 55125

  • CCOP - Main Line Health

    Wynnewood, Pennsylvania, 19096

  • Lankenau Cancer Center at Lankenau Hospital

    Wynnewood, Pennsylvania, 19096

  • Genesis - Good Samaritan Hospital

    Zanesville, Ohio, 43701

Other trials in United States

About this study

Official title: Phase II Study of Treatment Selection Based Upon Tumor Thymidylate Synthase Expression in Previously Untreated Patients With Metastatic Colorectal Cancer

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.

Read the 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.

Keywords
recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum
Medical subject headings
Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • bevacizumabBiological

    Also called NSC 704865, RhuMAb VEGF, Recombinant Humanized Monoclonal Anti-VEGF Antibody

    Given IV

  • fluorouracilDrug

    Also called 5-Fluorouracil, 5-FU, Adrucil, Efudex

    Given IV

  • irinotecan hydrochlorideDrug

    Also called Camptothecin-11, CPT-11, Camptosar

    Given IV

  • leucovorin calciumDrug

    Also called Leucovorin, Wellcovorin' citrovorum factor, folinic acid, 5-formyl tetrahydrofolate, LV, LCV.

    Given IV

  • OxaliplatinDrug

    Also called Eloxatin, trans-l-diaminocyclohexane oxalatoplatinum, cis-[oxalato(trans-l-1,2-diaminocyclohexane)platinum(II)].

    Given IV

Study groups in NCT00098787
Study groupRoleWhat they receive
Arm A (High TS, IROX/bev)ExperimentalPatients 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.
Receives: Biological: bevacizumab; Drug: irinotecan hydrochloride; Drug: Oxaliplatin
Arm B (High TS, FOLFOX/bev)ExperimentalPatients 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.
Receives: Biological: bevacizumab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: Oxaliplatin
Arm C (Low or intermediate TS, FOLFOX/bev)ExperimentalPatients with low or intermediate TS receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev) as in Arm B.
Receives: Biological: bevacizumab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: Oxaliplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate

    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.

    Measured: Assessed every 3 months if the patient is within 2 years of registration and every 6 months up to 4 years post-registration.

Secondary outcomes (2)

  1. Progression-Free Survival (PFS)

    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.

    Measured: 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.

  2. Overall Survival (OS)

    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.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2004 (estimated)
  2. Study start8 Sep 2005
  3. Primary completionNov 2013
  4. Study completionApr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
247 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00098787
Sponsor's protocol ID
CDR0000398096
Other IDs
E4203, U10CA021115
Status last verified
Jun 2023
First submitted
8 Dec 2004
Last updated
5 Jul 2023
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing bevacizumab, fluorouracil and irinotecan hydrochloride in people with Colorectal Cancer, run by Eastern Cooperative Oncology Group at 110 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 110 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00098787.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2023.

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