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Phase II Study of Irinotecan, Leucovorin, 5-Fluorouracil (FOLFIRI) Plus Bevacizumab as First-Line Treatment for Metastatic Colorectal Cancer

Phase 2
18 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

Phase II Study of Irinotecan, Leucovorin, 5-Fluorouracil (FOLFIRI) Plus Bevacizumab as First-Line Treatment for Metastatic Colorectal Cancer

Colorectal cancer growth may be affected by a protein in the body called "vascular
endothelial growth factor" (VEGF). A drug that blocks VEGF may be an effective treatment
for colorectal cancer. Bevacizumab is designed to block VEGF. Bevacizumab will be added to
5-Fluorouracil (5-FU), leucovorin (LV), and irinotecan, a drug combination routinely used in
the treatment of advanced colorectal cancer.

Before you can start treatment on the study, you will have what are called "screening
tests". These tests will help the doctor decide if you are eligible to take part in the
study. You will be asked questions about your medical history and about any medications you
are currently taking or have taken in the past. You will have a complete physical exam and
your heart rate, temperature, breathing rate, blood pressure, height, and weight will be
measured. You will be asked about your ability to perform every day activities. You will
have an electrocardiogram (ECG - a test that measures the electrical activity of the heart).
You will have a chest x-ray and scans (either computed tomography (CT) or magnetic
resonance imaging (MRI)) of your abdomen and pelvis to evaluate the cancer. Scans of other
parts of your body also may be taken if your doctor thinks they are needed to evaluate your
cancer. Blood (about 3 tablespoons) and urine samples will be collected for routine tests,
including complete blood count, carcinoembryonic antigen (CEA) level (a marker for your
cancer), and chemistry profile. Women who are able to have children must have a negative
blood or urine pregnancy test

If the screening evaluations show you are eligible to take part in the study, you may begin
treatment Study treatment is repeated every 2 weeks (14 days). Each 14-day period of
treatment is called a "cycle" of therapy. You must receive study treatment at M. D.

All study drugs will be given through a needle into a vein. For your first treatment, you
will receive bevacizumab alone first. The first dose of bevacizumab will be given over about
90 minutes. If you do not have a reaction (such as fever/chills), the next dose will be
given over about 60 minutes, and if again no reaction occurs, each dose after that will be
given over about 30 minutes. If you experience a reaction to the bevacizumab infusion, you
may be given acetaminophen (such as Tylenol) by mouth and/or an antihistamine by vein over
30 minutes before each dose to help decrease the risk of further reactions.

Fourteen (14) days later and for all future cycles, you will receive bevacizumab, LV, and
irinotecan given on Day 1 of each cycle. 5-FU is given over 46 hours over Days 1-3.

Bevacizumab will be given as described above. When the bevacizumab infusion ends, you will
receive LV and irinotecan, starting at the same time. You will receive irinotecan over 90
minutes and LV over 2 hours. When the LV infusion ends, 5-FU will be given over 2 to 4
minutes. This is followed by more 5-FU given over 46 hours using a small portable pump
(about the size of a standard paperback book).

Before each new cycle of study treatment, you will be asked questions about any side effects
you may have had and about any medications you are currently taking or have taken since you
last saw the study doctor. You will have a complete physical exam, including measurements of
blood pressure, pulse, temperature, and weight. You will be asked about your ability to
perform every day tasks. About 3 tablespoons of blood will be taken for routine laboratory
tests. These tests include a complete blood count and chemistry profile. A urine sample
will be taken before every other cycle of treatment. During the first cycle of treatment,
on Day 8, you will have a sample of blood (about 3 teaspoons) drawn. This test may be done
at a lab close to your home.

You will also have either CT scans or MRI of the tumor(s) every 8 weeks and at the end of
the study treatment. About 1 tablespoon of blood will be taken to check your CEA level at
the same time scans are done. Additional tests may be done during the study if your doctor
feels it is necessary for your care. Except for the weekly blood test, which may be done at
a lab close to home, all testing and evaluations must be done at M. D. Anderson.

If you experience severe side effects, treatment may be delayed, stopped, or you may receive
smaller doses of the treatment. You may continue to receive study treatment unless the
disease gets worse, you decide not to take part any longer, or your doctor decides it is in
your best interest to stop treatment.

When you stop study treatment, you will be asked to have some tests and evaluations done at
an end of study visit. Urine and about 3 tablespoons of blood will be taken for routine
laboratory tests, including complete blood count, CEA level, and chemistry profile. You will
also have a physical exam. CT scan or MRI scan of your abdomen and pelvis will also be
done to check the size and location of your disease.

Once you stop receiving study treatment, the study doctor or nurse will continue to check
how you are doing, either in the clinic or by telephone if you stop coming to M. D.
Anderson, every 3 months for the rest of your life.

This is an investigational study. The drugs used in this study are approved by the FDA for
treatment of advanced colorectal cancer. Up to 43 patients will take part in this
multicenter study. About 38 will be enrolled at M. D. Anderson.

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: ยท 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

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

15. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 0, unless affected area has been removed

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Median Progression-free Survival (PFS)

Outcome Description:

PFS is defined as the duration of time from start of treatment to time of disease progression using Kaplan-Meier median PFS time.

Outcome Time Frame:

From baseline until first documented progression or death from any cause, whichever came first, assessed up to 75 months

Safety Issue:


Principal Investigator

Scott Kopetz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

January 2005

Completion Date:

March 2011

Related Keywords:

  • Colorectal Cancer
  • Colorectal Cancer
  • Irinotecan
  • CPT-11
  • Leucovorin
  • LV
  • Folinic Acid
  • Fluorouracil
  • 5-FU
  • Adrucil
  • Efudex
  • Bevacizumab
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
  • Colorectal Neoplasms



UT MD Anderson Cancer CenterHouston, Texas  77030
Lyndon Baines Johnson General HospitalHouston, Texas  77030