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Study of FOLFIRI Plus Bevacizumab in Colorectal Cancer Patients

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00354978
First received: July 18, 2006
Last updated: September 14, 2011
Last verified: September 2011
  Purpose

Objectives:

  1. To estimate progression-free survival (PFS) at 12 months in subjects with metastatic colorectal cancer who receive FOLFIRI [folinic acid (leucovorin or LV), 5-Fluorouracil (5-FU), irinotecan) plus bevacizumab as first line treatment.
  2. To determine the objective response rate and the duration of objective response in this population.
  3. To assess overall survival (OS) in this population.
  4. To measure the effect of treatment on intratumoral blood volume and microvascular permeability by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in consenting patients in whom it is technically feasible.
  5. To correlate plasma proteomics with response.
  6. To assess the safety of this regimen.

Condition Intervention Phase
Colorectal Cancer
Drug: 5-Fluorouracil
Drug: Bevacizumab
Drug: Leucovorin
Drug: Irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Irinotecan, Leucovorin, 5-Fluorouracil (FOLFIRI) Plus Bevacizumab as First-Line Treatment for Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Median Progression-free Survival (PFS) [ Time Frame: From baseline until first documented progression or death from any cause, whichever came first, assessed up to 75 months ] [ Designated as safety issue: No ]
    PFS is defined as the duration of time from start of treatment to time of disease progression using Kaplan-Meier median PFS time.


Enrollment: 49
Study Start Date: January 2005
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFIRI plus Bevacizumab
FOLFIRI [folinic acid (leucovorin) 400 mg/m^2 by vein (IV) Day 1; 5-FU 400 mg/m^2 IV injection Day 1 immediately followed by 2.4 g/m^2 IV over 46 hours over Days 1-3; Irinotecan 180 mg/m^2 IV on Day 1] + Bevacizumab 5 mg/kg over 90 minutes on Day 1 administered alone then 5 mg/kg IV on Day 1 of 14 day cycle.
Drug: 5-Fluorouracil

400 mg/m^2 injection by vein Day 1 of 14 day cycle immediately after completion of leucovorin infusion.

2.4 g/m^2 by vein over 46 hours over Days 1-3 of 14 day cycle immediately after completion of 400 mg/m^2 injection.

Other Names:
  • F of FOLFIRI
  • 5-FU
  • Adrucil
  • Efudex
Drug: Bevacizumab

5 mg/kg over 90 minutes on Day 1 of first 14 day cycle as initial dose, administered alone without other drugs.

5 mg/kg by vein on Day 1 of 14 day cycle.

Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Leucovorin
400 mg/m^2 over 2-4 minutes by vein on Day 1 of 14 day cycle.
Other Names:
  • FOL of FOLFIRI
  • LV
  • folinic acid
Drug: Irinotecan
180 mg/m^2 by vein over 90 minutes on Day 1 of 14 day cycle.
Other Names:
  • IRI of FOLFIRI
  • CPT-11

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with metastatic disease documented on diagnostic imaging studies.
  2. Patient must have measurable lesions as defined by modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Patients who agree to undergo the optional Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) studies must have a metastatic liver lesion that is > 2 cm.
  3. Patient has not previously received chemotherapy for metastatic disease.
  4. Patient may have received adjuvant therapy for primary colorectal cancer provided that at least 6 months have elapsed from the time the adjuvant therapy was concluded and recurrent disease was documented.
  5. Written informed consent obtained.
  6. Age greater than/equal to 18 years.
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  8. Patients must have adequate organ and marrow function as defined below: · Absolute neutrophil count (ANC) greater than/equal to 1,500/mm3; platelets greater than/equal to 100,000/ mm3; hemoglobin greater than/equal to 9 gm/dL (may be transfused to maintain or exceed this level); total bilirubin less than/equal to 1.5 within institutional upper limit of normal (IULN); aspartate aminotransferase (AST or SGOT)/alanine aminotransferase (ALT or SGPT) less than/equal to 2.5 times IULN, or less than/equal to 5 times IULN if known liver metastases; serum creatinine less than/equal to 1.5 times IULN
  9. Patients must have an International Normalized Ratio (INR) less than/equal to 1.5 and a Partial thromboplastin time (PTT) less than/equal to IULN
  10. Patients with history of hypertension must be well-controlled (blood pressure less than/equal to 150/100), on a stable regimen of anti-hypertensive therapy.

Exclusion Criteria:

  1. Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental therapeutic drug study other than this protocol.
  2. Prior full field radiotherapy less than/equal to 4 weeks or limited field radiotherapy less than/equal to 2 weeks prior to treatment.
  3. History or presence of central nervous system metastases.
  4. Female patients who are pregnant or lactating or men and women of reproductive potential not willing to employ an effective method of birth control during treatment and for 3 months after discontinuing study treatment.
  5. A history of prior treatment with bevacizumab or other agents targeting Vascular endothelial growth factor (VEGF).
  6. Known dihydropyrimidine dehydrogenase deficiency.
  7. Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, irinotecan, 5-FU, or leucovorin.
  8. Serious non-healing wound, ulcer, or active bone fracture.
  9. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0; anticipation of need for major surgical procedure during the course of the study.
  10. Fine needle aspirations or core biopsies within 7days prior to Day 0.
  11. For patients who agree to Optional DCE-MRI studies: Cardiac pacemaker, neurostimulator, metal implants other than those specifically approved as safe for use in MR scanners at the magnetic field strength used for these studies, claustrophobia, obesity (weight exceeding equipment limits).
  12. Current or recent use of full-dose warfarin (except as required to maintain patency of preexisting, permanent indwelling IV catheters) for subjects receiving warfarin, INR should be < 1.5). Patients may have prophylactic use of low molecular weight heparin, however therapeutic use of heparin or low molecular weight heparin is not acceptable.
  13. Evidence of bleeding diathesis or coagulopathy.
  14. Patients with a history of another primary malignancy less than/equal to 5 years, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.
  15. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0, unless affected area has been removed surgically.
  16. Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen; Unstable angina; New York Heart Association (NYHA) greater than/equal to grade 2 congestive heart failure
  17. Myocardial infarction within 6 months of study enrollment; History of stroke within 6 months of study enrollment; Unstable symptomatic arrhythmia requiring medication (Patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible); Clinically significant peripheral vascular disease; Uncontrolled diabetes; Serious active or uncontrolled infection
  18. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
  19. Inability to comply with study and/or follow-up procedures.
  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: NCT00354978

Locations
United States, Texas
Lyndon Baines Johnson General Hospital
Houston, Texas, United States, 77030
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genentech, Inc.
Pfizer
Investigators
Principal Investigator: Scott Kopetz, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00354978     History of Changes
Other Study ID Numbers: 2004-0614
Study First Received: July 18, 2006
Results First Received: June 14, 2011
Last Updated: September 14, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Colorectal Cancer
FOLFIRI
Irinotecan
CPT-11
Leucovorin
LV
Folinic Acid
Fluorouracil
5-FU
Adrucil
Efudex
Bevacizumab
Avastin
Anti-VEGF monoclonal antibody
rhuMAb-VEGF

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Antibodies, Monoclonal
Bevacizumab
Fluorouracil
Folic Acid
Irinotecan
Levoleucovorin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antidotes
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Hematinics
Hematologic Agents
Immunologic Factors

ClinicalTrials.gov processed this record on November 20, 2014