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

Colorectal Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00101686
• Other study ID #: CPTAIV-0020-411
• Secondary ID: A5961021
• Status: Completed
• Phase: Phase 3
• First received: January 12, 2005
• Last updated: January 4, 2010
• Start date: February 2003
• Est. completion date: October 2008

Study information

• Verified date: January 2010
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 547
• Est. completion date: October 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

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).
• 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
• 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
• 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).
• 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).

Locations

Country	Name	City	State
Australia	Pfizer Investigational Site	Bedford Park	South Australia
Australia	Pfizer Investigational Site	Clayton	Victoria
Australia	Pfizer Investigational Site	Frankston	Victoria
Australia	Pfizer Investigational Site	South Brisbane	Queensland
Australia	Pfizer Investigational Site	Waratah	New South Wales
Australia	Pfizer Investigational Site	Woodville	South Australia
Canada	Pfizer Investigational Site	Brampton	Ontario
Canada	Pfizer Investigational Site	Chicoutimi	Quebec
Canada	Pfizer Investigational Site	Fleurimont	Quebec
Canada	Pfizer Investigational Site	Halifax	Nova Scotia
Canada	Pfizer Investigational Site	Kingston	Ontario
Canada	Pfizer Investigational Site	Kitchener	Ontario
Canada	Pfizer Investigational Site	Laval	Quebec
Canada	Pfizer Investigational Site	Mississauga	Ontario
Canada	Pfizer Investigational Site	Moncton	New Brunswick
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
Canada	Pfizer Investigational Site	Newmarket	Ontario
Canada	Pfizer Investigational Site	Oshawa	Ontario
Canada	Pfizer Investigational Site	Ottawa	Ontario
Canada	Pfizer Investigational Site	Quebec
Canada	Pfizer Investigational Site	Regina	Saskatchewan
Canada	Pfizer Investigational Site	Rimouski	Quebec
Canada	Pfizer Investigational Site	Saskatoon	Saskatchewan
Canada	Pfizer Investigational Site	Scarborough	Ontario
Canada	Pfizer Investigational Site	St. Johns	Newfoundland and Labrador
Canada	Pfizer Investigational Site	Sydney	Nova Scotia
Canada	Pfizer Investigational Site	Thunder Bay	Ontario
Canada	Pfizer Investigational Site	Windsor	Ontario
New Zealand	Pfizer Investigational Site	Auckland
New Zealand	Pfizer Investigational Site	Dunedin
New Zealand	Pfizer Investigational Site	Riccarton
New Zealand	Pfizer Investigational Site	Wellington
United States	Pfizer Investigational Site	Abilene	Texas
United States	Pfizer Investigational Site	Abington	Pennsylvania
United States	Pfizer Investigational Site	Albany	New York
United States	Pfizer Investigational Site	Albuquerque	New Mexico
United States	Pfizer Investigational Site	Alexandria	Louisiana
United States	Pfizer Investigational Site	Altamonte Springs	Florida
United States	Pfizer Investigational Site	Annapolis	Maryland
United States	Pfizer Investigational Site	Arlington	Texas
United States	Pfizer Investigational Site	Arroyo Grande	California
United States	Pfizer Investigational Site	Asheville	North Carolina
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Bangor	Maine
United States	Pfizer Investigational Site	Bartlesville	Oklahoma
United States	Pfizer Investigational Site	Beaumont	Texas
United States	Pfizer Investigational Site	Bedford	Texas
United States	Pfizer Investigational Site	Billings	Montana
United States	Pfizer Investigational Site	Birmgingham	Alabama
United States	Pfizer Investigational Site	Birmingham	Alabama
United States	Pfizer Investigational Site	Birmngham	Alabama
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Boulder	Colorado
United States	Pfizer Investigational Site	Burlington	Massachusetts
United States	Pfizer Investigational Site	Burnsville	Minnesota
United States	Pfizer Investigational Site	Cary	North Carolina
United States	Pfizer Investigational Site	Chattanooga	Tennessee
United States	Pfizer Investigational Site	Colchester	Vermont
United States	Pfizer Investigational Site	Collierville	Tennessee
United States	Pfizer Investigational Site	Columbia	Missouri
United States	Pfizer Investigational Site	Columbia	Missouri
United States	Pfizer Investigational Site	Columbus	Ohio
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dayton	Ohio
United States	Pfizer Investigational Site	Denton	Texas
United States	Pfizer Investigational Site	Edmonds	Washington
United States	Pfizer Investigational Site	El Paso	Texas
United States	Pfizer Investigational Site	El Paso	Texas
United States	Pfizer Investigational Site	Eugene	Oregon
United States	Pfizer Investigational Site	Fairfax	Virginia
United States	Pfizer Investigational Site	Farmington	New Mexico
United States	Pfizer Investigational Site	Fayetteville	North Carolina
United States	Pfizer Investigational Site	Fishers	Indiana
United States	Pfizer Investigational Site	Flagstaff	Arizona
United States	Pfizer Investigational Site	Fort Wayne	Indiana
United States	Pfizer Investigational Site	Fort Worth	Texas
United States	Pfizer Investigational Site	Fountian Valley	California
United States	Pfizer Investigational Site	Fredericksburg	Texas
United States	Pfizer Investigational Site	Fresno	California
United States	Pfizer Investigational Site	Garland	Texas
United States	Pfizer Investigational Site	Germantown	Tennessee
United States	Pfizer Investigational Site	Glendale	Wisconsin
United States	Pfizer Investigational Site	Grand Rapids	Michigan
United States	Pfizer Investigational Site	Greensboro	North Carolina
United States	Pfizer Investigational Site	Hendersonville	North Carolina
United States	Pfizer Investigational Site	Hickory	North Carolina
United States	Pfizer Investigational Site	Hollywood	Florida
United States	Pfizer Investigational Site	Hooksett	New Hampshire
United States	Pfizer Investigational Site	Hot Spring	Arkansas
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Houston	Texas
United States	Pfizer Investigational Site	Irving	Texas
United States	Pfizer Investigational Site	Jackson	Tennessee
United States	Pfizer Investigational Site	Joplin	Missouri
United States	Pfizer Investigational Site	Knoxville	Tennessee
United States	Pfizer Investigational Site	Knoxville	Tennessee
United States	Pfizer Investigational Site	Lacy	Washington
United States	Pfizer Investigational Site	Las Vegas	Nevada
United States	Pfizer Investigational Site	Lauderhill	Florida
United States	Pfizer Investigational Site	Lebanon	New Hampshire
United States	Pfizer Investigational Site	Lewisville	Texas
United States	Pfizer Investigational Site	Longview	Texas
United States	Pfizer Investigational Site	Los Gatos	California
United States	Pfizer Investigational Site	Macon	Georgia
United States	Pfizer Investigational Site	Manhaset	New York
United States	Pfizer Investigational Site	McAllen	Texas
United States	Pfizer Investigational Site	Mesquite	Texas
United States	Pfizer Investigational Site	Miami	Florida
United States	Pfizer Investigational Site	Miami Beach	Florida
United States	Pfizer Investigational Site	Midland	Texas
United States	Pfizer Investigational Site	Milwaukee	Wisconsin
United States	Pfizer Investigational Site	Mission Hills	California
United States	Pfizer Investigational Site	Mobile	Alabama
United States	Pfizer Investigational Site	Modesto	California
United States	Pfizer Investigational Site	Nashua	New Hampshire
United States	Pfizer Investigational Site	New Braunfels	Texas
United States	Pfizer Investigational Site	New Port Richey	Florida
United States	Pfizer Investigational Site	Newport News	Virginia
United States	Pfizer Investigational Site	Niles	Illinois
United States	Pfizer Investigational Site	Norman	Oklahoma
United States	Pfizer Investigational Site	Norwalk	Connecticut
United States	Pfizer Investigational Site	Ocala	Florida
United States	Pfizer Investigational Site	Odessa	Texas
United States	Pfizer Investigational Site	Oklahoma City	Oklahoma
United States	Pfizer Investigational Site	Omaha	Nebraska
United States	Pfizer Investigational Site	Orange	California
United States	Pfizer Investigational Site	Overland Park	Kansas
United States	Pfizer Investigational Site	Oxnard	California
United States	Pfizer Investigational Site	Paris	Texas
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Philadelphia	Pennsylvania
United States	Pfizer Investigational Site	Pittsfield	Massachusetts
United States	Pfizer Investigational Site	Portland	Oregon
United States	Pfizer Investigational Site	Reading	Pennsylvania
United States	Pfizer Investigational Site	Roanoke	Virginia
United States	Pfizer Investigational Site	Robbinsdale	Minnesota
United States	Pfizer Investigational Site	Rockford	Illinois
United States	Pfizer Investigational Site	Rockville Centre	New York
United States	Pfizer Investigational Site	San Diego	California
United States	Pfizer Investigational Site	San Jose	California
United States	Pfizer Investigational Site	Santa Fe	New Mexico
United States	Pfizer Investigational Site	Sarasota	Florida
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	Sedona	Arizona
United States	Pfizer Investigational Site	Sherman	Texas
United States	Pfizer Investigational Site	Shrevport	Louisiana
United States	Pfizer Investigational Site	Skokie	Illinois
United States	Pfizer Investigational Site	Spokane	Washington
United States	Pfizer Investigational Site	Springdale	Arkansas
United States	Pfizer Investigational Site	St. Louis	Missouri
United States	Pfizer Investigational Site	St. Louis	Missouri
United States	Pfizer Investigational Site	Stamford	Connecticut
United States	Pfizer Investigational Site	Summit	New Jersey
United States	Pfizer Investigational Site	Tamarac	Florida
United States	Pfizer Investigational Site	Temple	Texas
United States	Pfizer Investigational Site	Terre Haute	Indiana
United States	Pfizer Investigational Site	Tucson	Arizona
United States	Pfizer Investigational Site	Tyler	Texas
United States	Pfizer Investigational Site	Tyler	Texas
United States	Pfizer Investigational Site	Waco	Texas
United States	Pfizer Investigational Site	Washington	District of Columbia
United States	Pfizer Investigational Site	Webster	Texas
United States	Pfizer Investigational Site	Wichita Falls	Texas
United States	Pfizer Investigational Site	Winston-Salem	North Carolina
United States	Pfizer Investigational Site	Winston-Salem	North Carolina
United States	Pfizer Investigational Site	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL		every 6 weeks until disease progression	No
Secondary	Time to Progression: FOLFIRI, mIFL and CapeIRI		every 6 weeks until disease progression	No
Secondary	Overall Response: FOLFIRI, mIFL and CapeIRI		every 6 weeks during chemotherapy until disease progression	No
Secondary	Survival Time: FOLFIRI, mIFL and CapeIRI		assessed at least every week during treatment and at least every 3 months during follow-up	No
Secondary	1 Year Survival: FOLFIRI, mIFL and CapeIRI		1 year from date of randomization	No
Secondary	Time to Progression : Celecoxib and Placebo		every 6 weeks until disease progression	No
Secondary	Overall Response: Celecoxib and Placebo		every 6 weeks during chemotherapy until disease progression	No
Secondary	Survival Time: Celecoxib and Placebo		assessed at least every week during treatment and at least every 3 months during follow-up	No
Secondary	Time to Progression: Bevacizumab With FOLFIRI, mIFL		every 6 weeks until disease progression	No
Secondary	Overall Response: Bevacizumab With FOLFIRI, mIFL		every 6 weeks during chemotherapy until disease progression	No
Secondary	1 Year Survival: Bevacizumab With FOLFIRI, mIFL		1 year from date of randomization	No
Secondary	Survival Time at Last Follow-Up Visit: Bevacizumab With FOLFIRI, mIFL		Last Follow-Up Visit	No
Secondary	Dose Reduction Due to Treatment Emergent Adverse Events		Day 1; Day 8; and at end of every 3 treatment cycles for FOLFIRI; end of every 2 cycles for mIRI	No
Secondary	Overall Relative Dose Intensity of Irinotecan		End of treatment cycle	No