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

NCT00098787 | Completed Phase 2 Results DMC

• 3 other identifiers: CDR0000398096E4203U10CA021115
• Study Type: interventional
• Target: 247
• Locations: 1 country
• Sites: 110

Brief 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. 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.

Conditions

Colorectal Cancer

Keywords

recurrent colon cancer; stage IV colon cancer; recurrent rectal cancer; stage IV rectal cancer; adenocarcinoma of the colon; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (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.

  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)

• Progression-Free Survival (PFS)

  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.

• Overall Survival (OS)

  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.

Study Arms (3)

Arm A (High TS, IROX/bev)

EXPERIMENTAL

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; Drug: irinotecan hydrochloride; Drug: Oxaliplatin

Arm B (High TS, FOLFOX/bev)

EXPERIMENTAL

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; Drug: fluorouracil; Drug: leucovorin calcium; Drug: Oxaliplatin

Arm C (Low or intermediate TS, FOLFOX/bev)

EXPERIMENTAL

Patients with low or intermediate TS receive 5-Fluorouracil, leucovorin, oxaliplatin, and bevacizumab (FOLFOX/bev) as in Arm B.

Biological: bevacizumab; Drug: fluorouracil; Drug: leucovorin calcium; Drug: Oxaliplatin

Interventions

bevacizumab BIOLOGICAL

Given IV

Also known as: NSC 704865, RhuMAb VEGF, Recombinant Humanized Monoclonal Anti-VEGF Antibody

Arm A (High TS, IROX/bev); Arm B (High TS, FOLFOX/bev); Arm C (Low or intermediate TS, FOLFOX/bev)

fluorouracil DRUG

Given IV

Also known as: 5-Fluorouracil, 5-FU, Adrucil, Efudex

Arm B (High TS, FOLFOX/bev); Arm C (Low or intermediate TS, FOLFOX/bev)

irinotecan hydrochloride DRUG

Given IV

Also known as: Camptothecin-11, CPT-11, Camptosar

Arm A (High TS, IROX/bev)

leucovorin calcium DRUG

Given IV

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

Arm B (High TS, FOLFOX/bev); Arm C (Low or intermediate TS, FOLFOX/bev)

Oxaliplatin DRUG

Given IV

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

Arm A (High TS, IROX/bev); Arm B (High TS, FOLFOX/bev); Arm C (Low or intermediate TS, FOLFOX/bev)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Eastern Cooperative Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (110)

California Cancer Care, Incorporated - Greenbrae

Greenbrae, California, 94904, United States

Location

Aurora Presbyterian Hospital

Aurora, Colorado, 80012, United States

Location

Boulder Community Hospital

Boulder, Colorado, 80301-9019, United States

Location

Penrose Cancer Center at Penrose Hospital

Colorado Springs, Colorado, 80933, United States

Location

St. Anthony Central Hospital

Denver, Colorado, 80204, United States

Location

Porter Adventist Hospital

Denver, Colorado, 80210, United States

Location

Presbyterian - St. Luke's Medical Center

Denver, Colorado, 80218, United States

Location

St. Joseph Hospital

Denver, Colorado, 80218, United States

Location

Rose Medical Center

Denver, Colorado, 80220, United States

Location

CCOP - Colorado Cancer Research Program

Denver, Colorado, 80224-2522, United States

Location

Swedish Medical Center

Englewood, Colorado, 80110, United States

Location

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

Grand Junction, Colorado, 81502, United States

Location

North Colorado Medical Center

Greeley, Colorado, 80631, United States

Location

Littleton Adventist Hospital

Littleton, Colorado, 80122, United States

Location

Sky Ridge Medical Center

Lone Tree, Colorado, 80124, United States

Location

Hope Cancer Care Center at Longmont United Hospital

Longmont, Colorado, 80501, United States

Location

McKee Medical Center

Loveland, Colorado, 80539, United States

Location

Parker Adventist Hospital

Parker, Colorado, 80138, United States

Location

St. Mary - Corwin Regional Medical Center

Pueblo, Colorado, 81004, United States

Location

North Suburban Medical Center

Thornton, Colorado, 80229, United States

Location

Exempla Lutheran Medical Center

Wheat Ridge, Colorado, 80033, United States

Location

University of Florida Shands Cancer Center

Gainesville, Florida, 32610-0232, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Veterans Affairs Medical Center - Atlanta (Decatur)

Decatur, Georgia, 30033, United States

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

Hematology and Oncology Associates

Chicago, Illinois, 60611, United States

Location

Saint Joseph Hospital

Chicago, Illinois, 60657, United States

Location

Decatur Memorial Hospital Cancer Care Institute

Decatur, Illinois, 62526, United States

Location

Provena St. Mary's Regional Cancer Center - Kankakee

Kankakee, Illinois, 60901, United States

Location

North Shore Oncology and Hematology Associates, Limited - Libertyville

Libertyville, Illinois, 60048, United States

Location

Cancer Care and Hematology Specialists of Chicagoland - Niles

Niles, Illinois, 60714, United States

Location

Swedish-American Regional Cancer Center

Rockford, Illinois, 61104-2315, United States

Location

Hematology Oncology Associates - Skokie

Skokie, Illinois, 60076, United States

Location

Elkhart General Hospital

Elkhart, Indiana, 46515, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

Veterans Affairs Medical Center - Indianapolis

Indianapolis, Indiana, 46202, United States

Location

William N. Wishard Memorial Hospital

Indianapolis, Indiana, 46202, United States

Location

Howard Community Hospital

Kokomo, Indiana, 46904, United States

Location

Center for Cancer Therapy at LaPorte Hospital and Health Services

La Porte, Indiana, 46350, United States

Location

Saint Joseph Regional Medical Center

Mishawaka, Indiana, 46545-1470, United States

Location

CCOP - Northern Indiana CR Consortium

South Bend, Indiana, 46601, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

McCreery Cancer Center at Ottumwa Regional

Ottumwa, Iowa, 52501, United States

Location

Siouxland Hematology-Oncology Associates, LLP

Sioux City, Iowa, 51101, United States

Location

Mercy Medical Center - Sioux City

Sioux City, Iowa, 51102, United States

Location

St. Luke's Regional Medical Center

Sioux City, Iowa, 51104, United States

Location

Borgess Medical Center

Kalamazoo, Michigan, 49001, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007-3731, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

Lakeland Regional Cancer Care Center - St. Joseph

Saint Joseph, Michigan, 49085, United States

Location

Lakeside Cancer Specialists, PLLC

Saint Joseph, Michigan, 49085, United States

Location

MeritCare Bemidji

Bemidji, Minnesota, 56601, United States

Location

Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

Location

Mercy and Unity Cancer Center at Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

Location

Mercy and Unity Cancer Center at Unity Hospital

Fridley, Minnesota, 55432, United States

Location

Hutchinson Area Health Care

Hutchinson, Minnesota, 55350, United States

Location

HealthEast Cancer Care at St. John's Hospital

Maplewood, Minnesota, 55109, United States

Location

Minnesota Oncology - Maplewood

Maplewood, Minnesota, 55109, United States

Location

Virginia Piper Cancer Institute at Abbott - Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Hennepin County Medical Center - Minneapolis

Minneapolis, Minnesota, 55415, United States

Location

New Ulm Medical Center

New Ulm, Minnesota, 56073, United States

Location

Humphrey Cancer Center at North Memorial Outpatient Center

Robbinsdale, Minnesota, 55422-2900, United States

Location

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, 55416, United States

Location

Park Nicollet Cancer Center

Saint Louis Park, Minnesota, 55416, United States

Location

Regions Hospital Cancer Care Center

Saint Paul, Minnesota, 55101, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

St. Francis Cancer Center at St. Francis Medical Center

Shakopee, Minnesota, 55379, United States

Location

Lakeview Hospital

Stillwater, Minnesota, 55082, United States

Location

Ridgeview Medical Center

Waconia, Minnesota, 55387, United States

Location

Willmar Cancer Center at Rice Memorial Hospital

Willmar, Minnesota, 56201, United States

Location

Minnesota Oncology - Woodbury

Woodbury, Minnesota, 55125, United States

Location

Cancer Resource Center - Lincoln

Lincoln, Nebraska, 68510, United States

Location

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Immanuel Medical Center

Omaha, Nebraska, 68122, United States

Location

Alegant Health Cancer Center at Bergan Mercy Medical Center

Omaha, Nebraska, 68124, United States

Location

Lakeside Hospital

Omaha, Nebraska, 68130, United States

Location

Creighton University Medical Center

Omaha, Nebraska, 68131-2197, United States

Location

Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton

Marlton, New Jersey, 08053, United States

Location

CCOP - MeritCare Hospital

Fargo, North Dakota, 58122, United States

Location

Roger Maris Cancer Center at MeritCare Hospital

Fargo, North Dakota, 58122, United States

Location

Adena Regional Medical Center

Chillicothe, Ohio, 45601, United States

Location

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MetroHealth Cancer Care Center at MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Riverside Methodist Hospital Cancer Care

Columbus, Ohio, 43214-3998, United States

Location

CCOP - Columbus

Columbus, Ohio, 43215, United States

Location

Grant Medical Center Cancer Care

Columbus, Ohio, 43215, United States

Location

Mount Carmel Health - West Hospital

Columbus, Ohio, 43222, United States

Location

Doctors Hospital at Ohio Health

Columbus, Ohio, 43228, United States

Location

Grady Memorial Hospital

Delaware, Ohio, 43015, United States

Location

Fairfield Medical Center

Lancaster, Ohio, 43130, United States

Location

St. Rita's Medical Center

Lima, Ohio, 45801, United States

Location

Strecker Cancer Center at Marietta Memorial Hospital

Marietta, Ohio, 45750, United States

Location

Knox Community Hospital

Mount Vernon, Ohio, 43050, United States

Location

Licking Memorial Cancer Care Program at Licking Memorial Hospital

Newark, Ohio, 43055, United States

Location

Southern Ohio Medical Center Cancer Center

Portsmouth, Ohio, 45662, United States

Location

Community Hospital of Springfield and Clark County

Springfield, Ohio, 45505, United States

Location

Genesis - Good Samaritan Hospital

Zanesville, Ohio, 43701, United States

Location

Natalie Warren Bryant Cancer Center at St. Francis Hospital

Tulsa, Oklahoma, 74136, United States

Location

Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest

Allentown, Pennsylvania, 18105, United States

Location

Bryn Mawr Hospital

Bryn Mawr, Pennsylvania, 19010, United States

Location

Cancer Center of Paoli Memorial Hospital

Paoli, Pennsylvania, 19301-1792, United States

Location

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center

Reading, Pennsylvania, 19612-6052, United States

Location

CCOP - Main Line Health

Wynnewood, Pennsylvania, 19096, United States

Location

Lankenau Cancer Center at Lankenau Hospital

Wynnewood, Pennsylvania, 19096, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, 57117-5039, United States

Location

Erlanger Cancer Center at Erlanger Hospital - Baroness

Chattanooga, Tennessee, 37403, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Bevacizumab; Fluorouracil; Irinotecan; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Study Statistician
• Organization: Eastern Cooperative Oncology Group (ECOG) Statistical Office

617-632-3012

Study Officials

• Neal J. Meropol, MD

  Fox Chase Cancer Center

  STUDY CHAIR

• Jean L. Grem, MD

  University of Nebraska

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2004
• First Posted: December 9, 2004
• Study Start: September 8, 2005
• Primary Completion: November 1, 2013
• Study Completion: April 1, 2015
• Last Updated: July 5, 2023
• Results First Posted: June 27, 2014

Record last verified: 2023-06

Locations

US (110)