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Single-Institution Phase II Trial of Oxaliplatin, 5-Fluorouracil, Leucovorin and Bevacizumab (Folfox-B) for Initially Unresectable Colorectal Liver Metastases: Downstaging Followed By Hepatic Resection

Phase 2
18 Years
Not Enrolling
Colorectal Liver Metastases

Thank you

Trial Information

Single-Institution Phase II Trial of Oxaliplatin, 5-Fluorouracil, Leucovorin and Bevacizumab (Folfox-B) for Initially Unresectable Colorectal Liver Metastases: Downstaging Followed By Hepatic Resection

Oxaliplatin and bevacizumab are chemotherapy drugs that are designed to kill cancer cells.
5-FU is a chemotherapy drug that helps to stop the growth of cancer cells. Leucovorin is a
drug that may help increase the effect of 5-FU.

The study drugs will be given to you on an outpatient basis and will involve a minimum of 4
cycles and up to a maximum of 12 cycles of chemotherapy. All chemotherapy will be given
through a catheter placed in a vein in the shoulder in "cycles". Each "cycle" equals 14
days. On the first day (Day 1) of each cycle, bevacizumab will be given for 30 to 90 minutes
and oxaliplatin and leucovorin for 2 hours. On Day 1 as well, part of the total 5-FU dose
will be given for 15 minutes through the catheter. The rest of the 5-FU dose is then given
through a pump over the next 46 hours. After 46 hours, you will have a rest period, without
drug treatment for the rest of the cycle until the start of the next cycle.

Before each chemotherapy cycle, you will have blood drawn (about 2 tablespoons) for tests to
check for any side effects. Depending on the results of the blood tests, these blood tests
may be done more often. You will also have your vital signs (blood pressure, breathing,
temperature, and heart rate) monitored during the treatment. You will be seen every 2 weeks
by one of your doctors during your therapy.

If at any time the disease gets worse or you experience any intolerable side effects, you
will be taken off the study.

After completion of the 4th cycle of chemotherapy, you will have a complete physical exam
and routine blood tests (about 2 tablespoons). You will also have a CT scan of the abdomen
and pelvis and a chest x-ray or CT scan of the chest. These tests are being done to find
out if the tumor can be removed by surgery.

If your tumors cannot be removed at this time, you will continue to receive the same dose of
chemotherapy with the same tests for up to a maximum of 12 cycles. If it is found that the
tumor still cannot be removed after 12 cycles, your participation in this study will be
complete and your doctor will discuss other treatment options with you.

If the tumor can be removed, you will receive 1 additional cycle of oxaliplatin, leucovorin,
and 5-FU (no bevacizumab) at the same doses before you go on to have the surgery. Your
surgery will be scheduled 8-12 weeks after the completion of chemotherapy. The surgeon will
explain the surgery and any risks. During liver tumor surgery, normal tissue around the
edges of the tumor will be collected as part of routine care. You will be asked to sign a
separate consent form for the surgery. Additional routine blood tests (about 2 tablespoons)
and a PET scan will be done before surgery.

If you have tumors removed, around 28 days after the surgery, you will be given 8 additional
cycles of bevacizumab given the same way as before surgery.

Around 4-6 weeks after the final chemotherapy treatment, you will have follow-up CT scans of
the abdomen and pelvis, a chest x-ray or CT scan of the chest, and a routine blood test
(about 2 tablespoons). These tests will be repeated every 3 months for the first 3 years
after surgery, every 6 months for the 4th and 5th year after surgery, and then once a year
for the rest of your life. PET scans will be done once a year to check on the status of the

This is an investigational study. Oxaliplatin, 5-FU, leucovorin, and bevacizumab are FDA
approved and commercially available for the treatment of this disease. However, their use
together in this study is investigational. Up to 42 patients will take part in this study.
All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Patients must have hepatic colorectal metastasis confirmed by percutaneous or
intraoperative hepatic tumor biopsy.

2. Patients must have radiological evidence of measurable liver metastasis with helical
CT scan (1 cm or greater in greatest transverse dimension).

3. Patients with synchronous disease and resectable intact primary tumors are eligible.

4. Colorectal liver metastases will be determined to be unresectable by a surgeon with
expertise in hepatic surgery (equal to or greater than 10 resections performed in a
year). A patient is defined as unresectable when distribution and extent of disease
preclude margin negative resection (tumor contact with or involvement of all three
major hepatic veins or portal confluence or a combination of involvement of main
branches of portal veins and hepatic veins), but two adjacent hepatic segments with
adequate vascular inflow and outflow are relatively spared (contain 4 or fewer

5. Performance status: Zubrod 0 or 1.

6. Patients with a prior history of non-colorectal cancer may be included if there is no
evidence of malignancy for at least 5 years from last treatment and no evidence of
recurrence. In addition, patients with completely resected non-melanoma skin cancer
or cervical carcinoma in-situ may be included.

7. Radiological baseline studies shall be completed within 21 days of protocol

8. Laboratory data as follows (within 21 days of protocol registration): Adequate bone
marrow as evidenced by; Hemoglobin greater than or equal to 9.0 g %; White blood cell
count greater than or equal to 3,000 cells/mm; Platelet count greater than or equal
to 100,000 cells/mm(3); Absolute neutrophil count greater than or equal to

9. Continued from inclusion # 9: Laboratory data as follows (within 21 days of protocol
registration): Adequate renal function as evidenced by; Creatinine less than or equal
to 1.5 mg/dL or estimated creatinine clearance greater than or equal to 60 cc/min;
Urinalysis: less than or equal to trace proteinuria. If greater than trace
proteinuria exists, a 24- hour urine collection for assessment of protein must
demonstrate less than 500 mg of protein/24 hours.

10. Continued from inclusion #10: Laboratory data as follows (within 21 days of protocol
registration): Adequate hepatic function as evidenced by; Total Bilirubin less than
or equal to 2.0 mg %; Alanine aminotransferase less than or equal to 280 IU/L;
Aspartate aminotransferase less than or equal to 230 IU/L; International normalized
ratio less than or equal to 2.0.

11. Women must not be pregnant or lactating. Women of childbearing potential must have a
negative Beta-HCG serum pregnancy test and to refrain from breast-feeding, as
specified in the informed consent given the unknown risk of teratogenicity of agents
in the study. Patients of childbearing potential agree to use an effective form of
contraception during the study and for 90 days following the last dose of study

12. Age greater than or equal to 18 years.

13. Coumadin, 1 mg, for patency of central venous catheter or therapeutic doses of
coumadin (INR less than or equal to 3) permitted.

14. Patients or their legally authorized representative must agree to participate, be
able to read, understand and provide informed consent to participate in the trial.

15. Patients must be recovered from both acute and late effects of any prior surgery,
radiotherapy or other antineoplastic therapy.

Exclusion Criteria:

1. Patients with surgically resectable colorectal liver metastases.

2. Patients with evidence of unresectable extrahepatic disease.

3. Patients with CNS metastases.

4. Patients with diffusely distributed bilateral hepatic metastases without sparing of
two adjacent hepatic segments.

5. Patients who have previously undergone chemotherapy treatment for metastatic disease.

6. Patients who developed metastatic disease less than or equal to 6 months from
adjuvant chemotherapy for stage II or stage III colorectal cancer.

7. Patients who have ever received bevacizumab.

8. Previous or concurrent treatment of hepatic metastatic disease with resection,
radiotherapy, radiofrequency ablation, cryotherapy/other ablative techniques, or
hepatic artery infusion chemotherapy.

9. Patients who underwent a major invasive surgical procedure or open biopsy within 28
days prior to registration.

10. Patients who underwent colonoscopy, core biopsy, or fine needle aspiration within 7
days prior to registration.

11. Patients who had an arterial thromboembolic event, including transient ischemic
attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial
infarction (MI) within 12 months of registration. Patients must not have greater than
or equal to Grade 2 peripheral vascular disease.

12. Patients with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, cardiac disease NYHA class III or IV, unstable angina
pectoris, unstable cardiac arrhythmia or tachycardia (heart rate greater than or
equal to 100 beats per minute), poorly controlled hypertension (systolic blood
pressure greater than or equal to 200 mmHg or diastolic blood pressure greater than
or equal to 100 mmHg) or psychiatric illness/social situations that would limit
compliance with study requirements are excluded.

13. Patients with preexisting chronic hepatic disease (chronic active hepatitis B or C,
cirrhosis), which would preclude surgical resection of metastases.

14. Patients with known hypersensitivity to any of the components of oxaliplatin,
5-fluorouracil, leucovorin or bevacizumab (AVASTIN™).

15. Patients who have received chemotherapy within 30 days of the first scheduled day of
protocol treatment.

16. Patients who received radiotherapy within 4 weeks of trial entry.

17. Patients who are receiving concurrent investigational therapy or who have received
investigational therapy within 30 days of the first scheduled day of protocol
treatment (investigational therapy is defined as treatment for which there is
currently no regulatory authority approved indication).

18. Peripheral neuropathy greater than or equal to Grade 2.

19. Patients with an active infection or with a fever greater than or equal to 38.5
degrees C within 3 days of the first scheduled day of protocol treatment.

20. Patients with known autoimmune disease including HIV.

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:

Complete Gross Resection Rate

Outcome Description:

Complete gross resection rate for patients with initially unresectable hepatic colorectal metastasis who are treated with a combination of oxaliplatin/ 5-fluorouracil/ leucovorin/ bevacizumab (Number of Resectable versus Not Resectable Patients).

Outcome Time Frame:

Over 4 year study period

Safety Issue:


Principal Investigator

Eddie Abdalla, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

November 2005

Completion Date:

June 2009

Related Keywords:

  • Colorectal Liver Metastases
  • Colorectal Liver Metastases
  • Oxaliplatin
  • Eloxatin
  • Fluorouracil
  • Leucovorin
  • Bevacizumab
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
  • Folfox-B
  • 5-FU
  • Avastin
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Liver Neoplasms



U.T.M.D. Anderson Cancer Center Houston, Texas  77030