Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00098787
Recruitment Status : Completed
First Posted : December 9, 2004
Results First Posted : June 27, 2014
Last Update Posted : August 21, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Tracking Information
First Submitted Date  ICMJE December 8, 2004
First Posted Date  ICMJE December 9, 2004
Results First Submitted Date  ICMJE May 27, 2014
Results First Posted Date  ICMJE June 27, 2014
Last Update Posted Date August 21, 2018
Study Start Date  ICMJE July 2005
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2014)
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. ]
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2014)
  • 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. ]
    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. ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bevacizumab and Oxaliplatin Combined With Irinotecan or Leucovorin and Fluorouracil in Treating Patients With Metastatic or Recurrent Colorectal Cancer
Official Title  ICMJE Phase II Study of Treatment Selection Based Upon Tumor Thymidylate Synthase Expression in Previously Untreated Patients With Metastatic Colorectal Cancer
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer
Intervention  ICMJE
  • 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: irinotecan hydrochloride
    Given IV
    Other Name: Camptothecin-11, CPT-11, Camptosar
  • 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)].
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: bevacizumab
    • Drug: irinotecan hydrochloride
    • Drug: Oxaliplatin
  • 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.
    Interventions:
    • Biological: bevacizumab
    • Drug: fluorouracil
    • Drug: leucovorin calcium
    • Drug: Oxaliplatin
  • 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.
    Interventions:
    • Biological: bevacizumab
    • Drug: fluorouracil
    • Drug: leucovorin calcium
    • Drug: Oxaliplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 27, 2014)
247
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE April 2015
Actual Primary Completion Date November 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00098787
Other Study ID Numbers  ICMJE CDR0000398096
E4203 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
U10CA021115 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eastern Cooperative Oncology Group
Study Sponsor  ICMJE Eastern Cooperative Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Neal J. Meropol, MD Fox Chase Cancer Center
Study Chair: Jean L. Grem, MD University of Nebraska
PRS Account Eastern Cooperative Oncology Group
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP