Trial Of Irinotecan In Combination With Three Methods Of Administration Of Fluoropyrimidine.

A Randomized, Multi-Center Phase III Trial Of Irinotecan In Combination With Three Different Methods Of Administration Of Fluoropyrimidine: Infusional 5-FU (FOLFIRI), Modified-Bolus 5-FU (Day 1 & 8), And Oral Capecitabine (Day 1-14); With Celecoxib Versus Placebo As First-Line Treatment For Patients With Metastatic Colorectal Cancer Study Amended April 23, 2004 To Include Bevacizumab

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.

Study Overview

• Status: Completed
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: Modified Bolus 5-FU/LV with Irinotecan; Drug: FOLFIRI + bevacizumab; Drug: miFL + bevacizumab; Drug: Infusional 5-FU/LV with Irinotecan; Drug: Oral Capecitabine with Irinotecan

• Study Type: Interventional
• Enrollment (Actual): 547
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Waratah, New South Wales, Australia, 2298
      • Pfizer Investigational Site
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Pfizer Investigational Site
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Pfizer Investigational Site
    • Woodville, South Australia, Australia, 5011
      • Pfizer Investigational Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Pfizer Investigational Site
    • Frankston, Victoria, Australia, 3199
      • Pfizer Investigational Site
• Canada
  • Quebec, Canada
    • Pfizer Investigational Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Pfizer Investigational Site
  • Newfoundland and Labrador
    • St. Johns, Newfoundland and Labrador, Canada, A1B 3V76
      • Pfizer Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Pfizer Investigational Site
    • Sydney, Nova Scotia, Canada, B1P 1P3
      • Pfizer Investigational Site
  • Ontario
    • Brampton, Ontario, Canada, L6W 3X4
      • Pfizer Investigational Site
    • Kingston, Ontario, Canada, K7L 5P9
      • Pfizer Investigational Site
    • Kitchener, Ontario, Canada, N2G 1G3
      • Pfizer Investigational Site
    • Mississauga, Ontario, Canada, L5B 1B8
      • Pfizer Investigational Site
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Pfizer Investigational Site
    • Oshawa, Ontario, Canada, L1G 2B9
      • Pfizer Investigational Site
    • Ottawa, Ontario, Canada, K1H 1C4
      • Pfizer Investigational Site
    • Scarborough, Ontario, Canada, M1P 2V5
      • Pfizer Investigational Site
    • Thunder Bay, Ontario, Canada, P7A 7T1
      • Pfizer Investigational Site
    • Windsor, Ontario, Canada, N8W 2X3
      • Pfizer Investigational Site
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • Pfizer Investigational Site
    • Fleurimont, Quebec, Canada, J1H 5N4
      • Pfizer Investigational Site
    • Laval, Quebec, Canada, H7M 3L9
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2X 3J4
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H1T 4B3
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2W 1S6
      • Pfizer Investigational Site
    • Rimouski, Quebec, Canada, G5L 5T1
      • Pfizer Investigational Site
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Pfizer Investigational Site
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Pfizer Investigational Site
• New Zealand
  • Auckland, New Zealand, 1
    • Pfizer Investigational Site
  • Dunedin, New Zealand, 9001
    • Pfizer Investigational Site
  • Riccarton, New Zealand, 8020
    • Pfizer Investigational Site
  • Wellington, New Zealand, 6039
    • Pfizer Investigational Site
• United States
  • Alabama
    • Birmgingham, Alabama, United States, 35205
      • Pfizer Investigational Site
    • Birmingham, Alabama, United States, 35205
      • Pfizer Investigational Site
    • Birmngham, Alabama, United States, 35211
      • Pfizer Investigational Site
    • Mobile, Alabama, United States, 36608
      • Pfizer Investigational Site
  • Arizona
    • Flagstaff, Arizona, United States, 86001
      • Pfizer Investigational Site
    • Sedona, Arizona, United States, 86336
      • Pfizer Investigational Site
    • Tucson, Arizona, United States, 85712
      • Pfizer Investigational Site
  • Arkansas
    • Hot Spring, Arkansas, United States, 71913
      • Pfizer Investigational Site
    • Springdale, Arkansas, United States, 72764
      • Pfizer Investigational Site
  • California
    • Arroyo Grande, California, United States, 93420
      • Pfizer Investigational Site
    • Fountian Valley, California, United States, 92708
      • Pfizer Investigational Site
    • Fresno, California, United States, 93710
      • Pfizer Investigational Site
    • Los Gatos, California, United States, 95032
      • Pfizer Investigational Site
    • Mission Hills, California, United States, 91345
      • Pfizer Investigational Site
    • Modesto, California, United States, 95355
      • Pfizer Investigational Site
    • Orange, California, United States, 92868
      • Pfizer Investigational Site
    • Oxnard, California, United States, 93030
      • Pfizer Investigational Site
    • San Diego, California, United States, 92123
      • Pfizer Investigational Site
    • San Jose, California, United States, 95125
      • Pfizer Investigational Site
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Pfizer Investigational Site
  • Connecticut
    • Norwalk, Connecticut, United States, 06581
      • Pfizer Investigational Site
    • Stamford, Connecticut, United States, 06902-3628
      • Pfizer Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Pfizer Investigational Site
  • Florida
    • Altamonte Springs, Florida, United States, 32701
      • Pfizer Investigational Site
    • Hollywood, Florida, United States, 33021
      • Pfizer Investigational Site
    • Lauderhill, Florida, United States, 33319
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33133
      • Pfizer Investigational Site
    • Miami Beach, Florida, United States
      • Pfizer Investigational Site
    • New Port Richey, Florida, United States, 34652
      • Pfizer Investigational Site
    • Ocala, Florida, United States, 34474
      • Pfizer Investigational Site
    • Sarasota, Florida, United States, 34239
      • Pfizer Investigational Site
    • Tamarac, Florida, United States, 33321
      • Pfizer Investigational Site
  • Georgia
    • Macon, Georgia, United States, 31201
      • Pfizer Investigational Site
  • Illinois
    • Niles, Illinois, United States, 60714
      • Pfizer Investigational Site
    • Rockford, Illinois, United States, 61108-2472
      • Pfizer Investigational Site
    • Skokie, Illinois, United States, 60077
      • Pfizer Investigational Site
  • Indiana
    • Fishers, Indiana, United States, 46038
      • Pfizer Investigational Site
    • Fort Wayne, Indiana, United States, 46815
      • Pfizer Investigational Site
    • Terre Haute, Indiana, United States, 47802
      • Pfizer Investigational Site
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • Pfizer Investigational Site
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Pfizer Investigational Site
    • Shrevport, Louisiana, United States, 71101
      • Pfizer Investigational Site
  • Maine
    • Bangor, Maine, United States, 04401
      • Pfizer Investigational Site
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Pfizer Investigational Site
    • Boston, Massachusetts, United States, 02115
      • Pfizer Investigational Site
    • Boston, Massachusetts, United States, 02215
      • Pfizer Investigational Site
    • Burlington, Massachusetts, United States, 01805
      • Pfizer Investigational Site
    • Pittsfield, Massachusetts, United States, 01201
      • Pfizer Investigational Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49603
      • Pfizer Investigational Site
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Pfizer Investigational Site
    • Robbinsdale, Minnesota, United States, 55422
      • Pfizer Investigational Site
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Pfizer Investigational Site
    • Columbia, Missouri, United States, 65203
      • Pfizer Investigational Site
    • Joplin, Missouri, United States, 64804
      • Pfizer Investigational Site
    • St. Louis, Missouri, United States, 63141
      • Pfizer Investigational Site
    • St. Louis, Missouri, United States, 63136
      • Pfizer Investigational Site
  • Montana
    • Billings, Montana, United States, 59101
      • Pfizer Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Pfizer Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Pfizer Investigational Site
  • New Hampshire
    • Hooksett, New Hampshire, United States, 03106
      • Pfizer Investigational Site
    • Lebanon, New Hampshire, United States, 03756-0001
      • Pfizer Investigational Site
    • Nashua, New Hampshire, United States, 03060
      • Pfizer Investigational Site
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Pfizer Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Pfizer Investigational Site
    • Farmington, New Mexico, United States, 87401
      • Pfizer Investigational Site
    • Santa Fe, New Mexico, United States, 87501
      • Pfizer Investigational Site
  • New York
    • Albany, New York, United States, 12208
      • Pfizer Investigational Site
    • Manhaset, New York, United States, 11030
      • Pfizer Investigational Site
    • Rockville Centre, New York, United States, 11570
      • Pfizer Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Pfizer Investigational Site
    • Cary, North Carolina, United States, 27511
      • Pfizer Investigational Site
    • Fayetteville, North Carolina, United States, 28302-2000
      • Pfizer Investigational Site
    • Greensboro, North Carolina, United States, 27403
      • Pfizer Investigational Site
    • Hendersonville, North Carolina, United States, 28791
      • Pfizer Investigational Site
    • Hickory, North Carolina, United States, 28602
      • Pfizer Investigational Site
    • Winston-Salem, North Carolina, United States, 27157
      • Pfizer Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • Pfizer Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Pfizer Investigational Site
    • Dayton, Ohio, United States, 45409
      • Pfizer Investigational Site
  • Oklahoma
    • Bartlesville, Oklahoma, United States, 74006
      • Pfizer Investigational Site
    • Norman, Oklahoma, United States, 73071
      • Pfizer Investigational Site
    • Oklahoma City, Oklahoma, United States, 73104
      • Pfizer Investigational Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Pfizer Investigational Site
    • Portland, Oregon, United States, 97213
      • Pfizer Investigational Site
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19141
      • Pfizer Investigational Site
    • Philadelphia, Pennsylvania, United States, 19014-4283
      • Pfizer Investigational Site
    • Reading, Pennsylvania, United States, 19603
      • Pfizer Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Pfizer Investigational Site
    • Collierville, Tennessee, United States, 38017
      • Pfizer Investigational Site
    • Germantown, Tennessee, United States, 38138
      • Pfizer Investigational Site
    • Jackson, Tennessee, United States, 38301
      • Pfizer Investigational Site
    • Knoxville, Tennessee, United States, 37920
      • Pfizer Investigational Site
    • Knoxville, Tennessee, United States, 37916
      • Pfizer Investigational Site
  • Texas
    • Abilene, Texas, United States, 79606-5208
      • Pfizer Investigational Site
    • Arlington, Texas, United States, 76012
      • Pfizer Investigational Site
    • Austin, Texas, United States, 78705
      • Pfizer Investigational Site
    • Austin, Texas, United States, 78731
      • Pfizer Investigational Site
    • Beaumont, Texas, United States, 77702-1449
      • Pfizer Investigational Site
    • Bedford, Texas, United States, 76022
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75230-2510
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75246
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75237
      • Pfizer Investigational Site
    • Dallas, Texas, United States, 75231-4400
      • Pfizer Investigational Site
    • Denton, Texas, United States, 76210
      • Pfizer Investigational Site
    • El Paso, Texas, United States, 79902
      • Pfizer Investigational Site
    • El Paso, Texas, United States, 79915
      • Pfizer Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Pfizer Investigational Site
    • Fredericksburg, Texas, United States, 78624-3847
      • Pfizer Investigational Site
    • Garland, Texas, United States, 75042
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77030
      • Pfizer Investigational Site
    • Houston, Texas, United States, 77054
      • Pfizer Investigational Site
    • Irving, Texas, United States, 75061-224
      • Pfizer Investigational Site
    • Lewisville, Texas, United States, 75067
      • Pfizer Investigational Site
    • Longview, Texas, United States, 75601
      • Pfizer Investigational Site
    • McAllen, Texas, United States, 78503
      • Pfizer Investigational Site
    • Mesquite, Texas, United States, 75050
      • Pfizer Investigational Site
    • Midland, Texas, United States, 79701
      • Pfizer Investigational Site
    • New Braunfels, Texas, United States, 78130
      • Pfizer Investigational Site
    • Odessa, Texas, United States, 79761
      • Pfizer Investigational Site
    • Paris, Texas, United States, 75460
      • Pfizer Investigational Site
    • Sherman, Texas, United States, 75090-0504
      • Pfizer Investigational Site
    • Temple, Texas, United States, 76508
      • Pfizer Investigational Site
    • Tyler, Texas, United States, 75702
      • Pfizer Investigational Site
    • Tyler, Texas, United States, 75701-2001
      • Pfizer Investigational Site
    • Waco, Texas, United States, 76712
      • Pfizer Investigational Site
    • Webster, Texas, United States, 77598
      • Pfizer Investigational Site
    • Wichita Falls, Texas, United States, 76310
      • Pfizer Investigational Site
  • Vermont
    • Colchester, Vermont, United States, 05446
      • Pfizer Investigational Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Pfizer Investigational Site
    • Newport News, Virginia, United States, 23606
      • Pfizer Investigational Site
    • Roanoke, Virginia, United States, 24014
      • Pfizer Investigational Site
  • Washington
    • Edmonds, Washington, United States, 98026
      • Pfizer Investigational Site
    • Lacy, Washington, United States, 98503
      • Pfizer Investigational Site
    • Seattle, Washington, United States, 98133
      • Pfizer Investigational Site
    • Spokane, Washington, United States, 99202
      • Pfizer Investigational Site
    • Yakima, Washington, United States, 98902
      • Pfizer Investigational Site
  • Wisconsin
    • Glendale, Wisconsin, United States, 53212
      • Pfizer Investigational Site
    • Milwaukee, Wisconsin, United States, 53226
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Modified Bolus 5-FU/LV with Irinotecan	Drug: Modified Bolus 5-FU/LV with Irinotecan; 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).
Experimental: FOLFIRI + bevacizumab	Drug: FOLFIRI + bevacizumab; 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
Experimental: miFL + bevacizumab	Drug: miFL + bevacizumab; 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
Experimental: Infusional 5-FU/LV with Irinotecan	Drug: Infusional 5-FU/LV with Irinotecan; 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).
Other: Oral Capecitabine with Irinotecan	Drug: Oral Capecitabine with Irinotecan; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL	Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).	every 6 weeks until disease progression

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression: FOLFIRI, mIFL and CapeIRI	Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).	every 6 weeks until disease progression
Overall Response: FOLFIRI, mIFL and CapeIRI	A subject will be considered achieving an overall response if the subject has a sustained Complete Response (CR) or Partial Response (PR) for at least 4 weeks, confirmed by tumor assessments. (CR: Disappearance of all target lesions. PR: greater than or equal to 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the Pre-treatment sum LD. )	every 6 weeks during chemotherapy until disease progression
Survival Time: FOLFIRI, mIFL and CapeIRI	Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.	assessed at least every week during treatment and at least every 3 months during follow-up
1 Year Survival: FOLFIRI, mIFL and CapeIRI	Number of patients alive or dead at 1 year. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.	1 year from date of randomization
Time to Progression : Celecoxib and Placebo	Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).	every 6 weeks until disease progression
Overall Response: Celecoxib and Placebo	A subject will be considered achieving an overall response if the subject has a sustained CR or PR for at least 4 weeks, confirmed by tumor assessments. (Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥ 30% decrease in the sum of the LD of target lesions, taking as reference the Pre-treatment sum LD. )	every 6 weeks during chemotherapy until disease progression
Survival Time: Celecoxib and Placebo	Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.	assessed at least every week during treatment and at least every 3 months during follow-up
Time to Progression: Bevacizumab With FOLFIRI, mIFL	Time to disease progression is defined as the number of months from date of randomization to the date of first documentation of disease progression (PD).	every 6 weeks until disease progression
Overall Response: Bevacizumab With FOLFIRI, mIFL	A subject will be considered achieving an overall response if the subject has a sustained CR or PR for at least 4 weeks, confirmed by tumor assessments. (Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): ≥ 30% decrease in the sum of the LD of target lesions, taking as reference the Pre-treatment sum LD. )	every 6 weeks during chemotherapy until disease progression
1 Year Survival: Bevacizumab With FOLFIRI, mIFL	Number of patients alive or dead at 1 year. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive.	1 year from date of randomization
Survival Time at Last Follow-Up Visit: Bevacizumab With FOLFIRI, mIFL	Survival time defined as time from date of randomization to date of death. In the absence of confirmation of death, survival time was censored to last date the subject known to be alive. Zero subjects analyzed indicates median could not be analyzed based on number of subjects who died.	Last Follow-Up Visit
Dose Reduction Due to Treatment Emergent Adverse Events	Number of subjects that had at least one Treatment-Emergent Adverse Event (TEAE) that led to a dose reduction. TEAE includes all reported Adverse Events that occurred within 30 days of last study medication.	Day 1; Day 8; and at end of every 3 treatment cycles for FOLFIRI; end of every 2 cycles for mIRI
Overall Relative Dose Intensity of Irinotecan	Relative dose intensity for a cycle was calculated as the percentage of the actual dose intensity of the cycle divided by the planned dose intensity of the cycle. Overall relative dose intensity was calculated as the average relative dose intensities over all cycles. (Dose intensity for each cycle was calculated as the actual dose level of the study medication received in that cycle divided by the number of weeks in the cycle.)	End of treatment cycle

Collaborators and Investigators

• Sponsor: Pfizer

Study record dates

Study Major Dates

• Study Start: February 1, 2003
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: January 12, 2005
• First Submitted That Met QC Criteria: January 12, 2005
• First Posted (Estimate): January 13, 2005

Study Record Updates

• Last Update Posted (Estimate): January 12, 2010
• Last Update Submitted That Met QC Criteria: January 4, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Capecitabine; Bevacizumab; Irinotecan
• Other Study ID Numbers: CPTAIV-0020-411; A5961021