Folfox-B Study for Patients With Colorectal Liver Metastases

This study has been terminated.
(Slow accrual, study terminated.)
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00508872
First received: July 27, 2007
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

Objective:

  • To evaluate the efficacy of the use of the combination of oxaliplatin, 5-fluorouracil, leucovorin and bevacizumab (FOLFOX-B) in patients with unresectable colorectal liver metastases, with the objective to downstage hepatic disease and enable complete resection of residual disease.

Primary Objective:

  • To evaluate the resection rate in patients with initially unresectable hepatic colorectal metastases downstaged with FOLFOX-B. Complete resection of all liver lesions is the goal.

Secondary Objectives:

  • To evaluate the probability of complete response, partial response or stable disease.
  • To evaluate the proportion of patients who are resected, and the proportion of patients achieving an R0 resection (among those receiving surgery).
  • To correlate survival with downstaging and resection based on metastatic colorectal prognostic score.
  • To evaluate the disease-free survival and overall survival.
  • To evaluate the positron emission tomography response rate.
  • To explore correlations of clinical response with telomerase and hTERT expression.

Condition Intervention Phase
Colorectal Liver Metastases
Drug: 5-Fluorouracil
Drug: Bevacizumab
Drug: Leucovorin
Drug: Oxaliplatin
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: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Complete Gross Resection Rate [ Time Frame: Over 4 year study period ] [ Designated as safety issue: No ]
    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).


Enrollment: 2
Study Start Date: November 2005
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FOLFOX-B
FOLFOX-B: 5-Fluorouracil 400 mg/m^2 IV + Bevacizumab 5 mg/kg IV + Leucovorin 400 mg/m^2 IV + Oxaliplatin 85 mg/m^2 IV
Drug: 5-Fluorouracil
400 mg/m^2 IV over 15 minutes, followed by 2400 mg/m^2 IV Over 46 Hours
Other Names:
  • 5-FU
  • Adrucil
  • Efudex
Drug: Bevacizumab
5 mg/kg IV Over 30-90 Minutes On Day 1 Every 14 Days
Other Names:
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
Drug: Leucovorin
400 mg/m^2 IV Over 2 Hours On Day 1 Every 14 Days
Other Names:
  • Citrovorum
  • Wellcovorin
Drug: Oxaliplatin
85 mg/m^2 IV Over 2 Hours On Day 1 Every 14 Days
Other Name: Eloxatin

  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. 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 lesions).
  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 registration.
  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 1500/mm(3).
  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 medication.
  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.
  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: NCT00508872

Locations
United States, Texas
U.T.M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Sanofi
Investigators
Principal Investigator: Eddie Abdalla, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00508872     History of Changes
Other Study ID Numbers: 2004-0816
Study First Received: July 27, 2007
Results First Received: October 8, 2010
Last Updated: July 27, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Colorectal Liver Metastases
Oxaliplatin
Eloxatin
Fluorouracil
Leucovorin
Bevacizumab
Anti-VEGF monoclonal antibody
rhuMAb-VEGF
Folfox-B
5-FU
Avastin

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Liver Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antibodies
Antibodies, Monoclonal
Fluorouracil
Oxaliplatin
Bevacizumab
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on August 26, 2014