Trial Of Irinotecan In Combination With Three Methods Of Administration Of Fluoropyrimidine.
Condition: Colorectal Neoplasms
MeSH terms: Colorectal Neoplasms
Intervention: Modified Bolus 5-FU/LV with Irinotecan; FOLFIRI + bevacizumab; miFL + bevacizumab; Infusional 5-FU/LV with Irinotecan; Oral Capecitabine with Irinotecan
Intervention description: Day 1 & 8: Irinotecan (125 mg/m2 IV over 90 minutes), LV (20 mg/m2 IV bolus), 5-FU (500 mg/m2 IV bolus). All chemotherapy cycles repeated every 3 weeks. Celecoxib/placebo treatment will commence on the same day as chemotherapy treatment (i.e. Day 1 of treatment on study). Celecoxib/placebo will be taken at a dose of 400 mg po BID [two times a day] (800 mg/day) and will continue daily without interruption (no rest period for celecoxib/placebo treatment).; Day 1 Bevacizumab 5mg/kg IV 90 minutes prior to irinotecan/LV Irinotecan 180 mg/m2 IV 90 minutes Leucovorin 400 mg/m2 IV 2 hours - given with irinotecan without mixing.
I m m e d i a t e l y f o l l o w e d b y :
5-FU 400 mg/m2 IV bolus 5-FU 2400 mg/m2 IV Continuous infusion over 46 hours Every 2 weeks
Amendment 2 Bevacizumab 5mg/kg IV 90 minutes prior to irinotecan/LV Irinotecan 180 mg/m2 IV 90 minutes Leucovorin 400 mg/m2 IV 2 hours - given with irinotecan without mixing.
I m m e d i a t e l y f o l l o w e d b y :
5-FU 400 mg/m2 IV bolus 5-FU 2400 mg/m2 IV Continuous infusion over 46 hours Celecoxib/placebo 400 mg BID [two times a day] oral Every 2 weeks; Day 1 Bevacizumab 7.5mg/kg IV *over 90 minutes - given prior to irinotecan, 5-FU, and leucovorin Irinotecan 125 mg/m2 IV over 90 minutes Leucovorin 20 mg/m2 IV bolus 5-FU 500 mg/m2 IV bolus Day 8 Irinotecan 125 mg/m2 IV over 90 minutes Leucovorin 20 mg/m2 IV bolus 5-FU 500 mg/m2 IV bolus Every 3 weeks Amendment 2 Day 1 Bevacizumab 7.5mg/kg IV over 90 minutes - given prior to irinotecan, 5-FU, and leucovorin Irinotecan 125 mg/m2 IV over 90 minutes Leucovorin 20 mg/m2 IV bolus 5-FU 500 mg/m2 IV bolus Celecoxib/placebo 400 mg BID [two times a day] oral Day 8 Irinotecan 125 mg/m2 IV over 90 minutes Leucovorin 20 mg/m2 IV bolus 5-FU 500 mg/m2 IV bolus Celecoxib/placebo -- 400 mg po BID [two times a day] continues daily without interruption Every 3 weeks; Day 1: Irinotecan (180 mg/m2) IV over 90 minutes, LV (racemic mixture 400 mg/m2) over 2 hours during irinotecan infusion but without mixing, immediately followed by 5-FU IV bolus (400 mg/m2) and 5-FU continuous infusion (2400 mg/m2) over 46 hours. FOLFIRI regimen is repeated every 2 weeks. Celecoxib/placebo treatment will commence on the same day at a dose of 400 mg po BID [two times a day](800 mg/day) and will continue daily without interruption (no rest period for celecoxib/placebo treatment).; Day 1: Irinotecan (250 mg/m2 IV) over 90 minutes; Day 1-14: capecitabine 1000 mg/m2 PO BID [two times a day] (28 single doses). All chemotherapy cycles repeated every 3 weeks. Celecoxib/placebo treatment will commence on the same day as chemotherapy treatment (i.e. Day 1 of treatment on study). Celecoxib/placebo will be taken at a dose of 400 mg po BID (800 mg/day) and will continue daily without interruption (no rest period for celecoxib/placebo treatment).
Intervention MeSH terms: Bevacizumab; Capecitabine; Irinotecan; Fluorouracil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 547.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study compares in the first study period combination of Irinotecan with three different
      methods of administration by Fluoropyrimidine. (ie. infusion, bolus and oral). In the second
      period of study it compares FOLFIRI [a chemotherapy regime that combines bolus irinotecan and
      leucovorin [LV] with infusional 5-fluorouracil (5-FU)] + bevacizumab and mlFL + bevacizumab.
      Measures of efficacy and safety will be reported.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of colorectal cancer (either newly diagnosed or recurrent disease) with
             evidence of metastatic disease. (Stage IV distant disease)

          -  Present or past histological documentation of adenocarcinoma of the colon or rectum.
             The site of the primary lesion must be or have been confirmed endoscopically,
             radiologically, or surgically to be or have been in the large bowel. Patients with a
             history of colorectal cancer treated by surgical resection who develop radiological or
             clinical evidence of metastatic cancer do not require separate histological or
             cytological confirmation of metastatic disease unless:

          -  An interval of greater than five years has elapsed between the primary surgery and the
             development of metastatic disease.

          -  The primary cancer was a Duke's A or B1.

          -  Physicians should consider biopsy of lesions to establish the diagnosis of metastatic
             colorectal cancer in each case if there is substantial clinical ambiguity regarding
             the nature of source of apparent metastases.

        Exclusion Criteria:

          -  Patients who received any prior systemic anticancer therapy for metastatic colorectal
             cancer (e.g., chemotherapy, antibody therapy, immunotherapy, gene therapy, vaccine
             therapy, cytokine therapy, or other experimental agents).

          -  Patients cannot have concurrent malignancies at study entry.

          -  Exceptions: Patients with prior non-colorectal malignancies will be eligible if they
             have been disease-free for ³ 3 years or are deemed at low risk for recurrence by their
             treating physician (e.g., early stage prostate cancer, melanoma or bladder cancer).
             Patients with squamous or basal cell carcinoma of the skin or in situ cervical cancer
             that have been effectively treated are eligible, even if these were diagnosed within 3
             years before randomization.