Study of FOLFIRI Plus Bevacizumab in Colorectal Cancer Patients
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: 5-Fluorouracil; Bevacizumab; Leucovorin; Irinotecan
Intervention description: 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.; 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.; 400 mg/m^2 over 2-4 minutes by vein on Day 1 of 14 day cycle.; 180 mg/m^2 by vein over 90 minutes on Day 1 of 14 day cycle.
Intervention MeSH terms: Leucovorin; Bevacizumab; Fluorouracil; Irinotecan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Colorectal Cancer; FOLFIRI; Irinotecan; CPT-11; Leucovorin; LV; Folinic Acid; Fluorouracil; 5-FU; Adrucil; Efudex; Bevacizumab; Avastin; Anti-VEGF monoclonal antibody; rhuMAb-VEGF

Summary:

      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.
    

Eligibility 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.