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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00101686




Registration number
NCT00101686
Ethics application status
Date submitted
12/01/2005
Date registered
13/01/2005
Date last updated
12/01/2010

Titles & IDs
Public title
Trial Of Irinotecan In Combination With Three Methods Of Administration Of Fluoropyrimidine.
Scientific 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
Secondary ID [1] 0 0
A5961021
Secondary ID [2] 0 0
CPTAIV-0020-411
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Modified Bolus 5-FU/LV with Irinotecan
Treatment: Drugs - FOLFIRI + bevacizumab
Treatment: Drugs - miFL + bevacizumab
Treatment: Drugs - Infusional 5-FU/LV with Irinotecan
Treatment: Drugs - Oral Capecitabine with Irinotecan

Experimental: Modified Bolus 5-FU/LV with Irinotecan -

Experimental: FOLFIRI + bevacizumab -

Experimental: miFL + bevacizumab -

Experimental: Infusional 5-FU/LV with Irinotecan -

Other: Oral Capecitabine with Irinotecan -


Treatment: Drugs: 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).

Treatment: Drugs: 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

Treatment: Drugs: 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

Treatment: Drugs: 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).

Treatment: Drugs: 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).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL
Timepoint [1] 0 0
every 6 weeks until disease progression
Secondary outcome [1] 0 0
Time to Progression: FOLFIRI, mIFL and CapeIRI
Timepoint [1] 0 0
every 6 weeks until disease progression
Secondary outcome [2] 0 0
Overall Response: FOLFIRI, mIFL and CapeIRI
Timepoint [2] 0 0
every 6 weeks during chemotherapy until disease progression
Secondary outcome [3] 0 0
Survival Time: FOLFIRI, mIFL and CapeIRI
Timepoint [3] 0 0
assessed at least every week during treatment and at least every 3 months during follow-up
Secondary outcome [4] 0 0
1 Year Survival: FOLFIRI, mIFL and CapeIRI
Timepoint [4] 0 0
1 year from date of randomization
Secondary outcome [5] 0 0
Time to Progression : Celecoxib and Placebo
Timepoint [5] 0 0
every 6 weeks until disease progression
Secondary outcome [6] 0 0
Overall Response: Celecoxib and Placebo
Timepoint [6] 0 0
every 6 weeks during chemotherapy until disease progression
Secondary outcome [7] 0 0
Survival Time: Celecoxib and Placebo
Timepoint [7] 0 0
assessed at least every week during treatment and at least every 3 months during follow-up
Secondary outcome [8] 0 0
Time to Progression: Bevacizumab With FOLFIRI, mIFL
Timepoint [8] 0 0
every 6 weeks until disease progression
Secondary outcome [9] 0 0
Overall Response: Bevacizumab With FOLFIRI, mIFL
Timepoint [9] 0 0
every 6 weeks during chemotherapy until disease progression
Secondary outcome [10] 0 0
1 Year Survival: Bevacizumab With FOLFIRI, mIFL
Timepoint [10] 0 0
1 year from date of randomization
Secondary outcome [11] 0 0
Survival Time at Last Follow-Up Visit: Bevacizumab With FOLFIRI, mIFL
Timepoint [11] 0 0
Last Follow-Up Visit
Secondary outcome [12] 0 0
Dose Reduction Due to Treatment Emergent Adverse Events
Timepoint [12] 0 0
Day 1; Day 8; and at end of every 3 treatment cycles for FOLFIRI; end of every 2 cycles for mIRI
Secondary outcome [13] 0 0
Overall Relative Dose Intensity of Irinotecan
Timepoint [13] 0 0
End of treatment cycle

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2008
Sample size
Target
Accrual to date
Final
547
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Waratah
Recruitment hospital [2] 0 0
Pfizer Investigational Site - South Brisbane
Recruitment hospital [3] 0 0
Pfizer Investigational Site - Bedford Park
Recruitment hospital [4] 0 0
Pfizer Investigational Site - Woodville
Recruitment hospital [5] 0 0
Pfizer Investigational Site - Clayton
Recruitment hospital [6] 0 0
Pfizer Investigational Site - Frankston
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Illinois
Country [11] 0 0
United States of America
State/province [11] 0 0
Indiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Kansas
Country [13] 0 0
United States of America
State/province [13] 0 0
Louisiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Maine
Country [15] 0 0
United States of America
State/province [15] 0 0
Maryland
Country [16] 0 0
United States of America
State/province [16] 0 0
Massachusetts
Country [17] 0 0
United States of America
State/province [17] 0 0
Michigan
Country [18] 0 0
United States of America
State/province [18] 0 0
Minnesota
Country [19] 0 0
United States of America
State/province [19] 0 0
Missouri
Country [20] 0 0
United States of America
State/province [20] 0 0
Montana
Country [21] 0 0
United States of America
State/province [21] 0 0
Nebraska
Country [22] 0 0
United States of America
State/province [22] 0 0
Nevada
Country [23] 0 0
United States of America
State/province [23] 0 0
New Hampshire
Country [24] 0 0
United States of America
State/province [24] 0 0
New Jersey
Country [25] 0 0
United States of America
State/province [25] 0 0
New Mexico
Country [26] 0 0
United States of America
State/province [26] 0 0
New York
Country [27] 0 0
United States of America
State/province [27] 0 0
North Carolina
Country [28] 0 0
United States of America
State/province [28] 0 0
Ohio
Country [29] 0 0
United States of America
State/province [29] 0 0
Oklahoma
Country [30] 0 0
United States of America
State/province [30] 0 0
Oregon
Country [31] 0 0
United States of America
State/province [31] 0 0
Pennsylvania
Country [32] 0 0
United States of America
State/province [32] 0 0
Tennessee
Country [33] 0 0
United States of America
State/province [33] 0 0
Texas
Country [34] 0 0
United States of America
State/province [34] 0 0
Vermont
Country [35] 0 0
United States of America
State/province [35] 0 0
Virginia
Country [36] 0 0
United States of America
State/province [36] 0 0
Washington
Country [37] 0 0
United States of America
State/province [37] 0 0
Wisconsin
Country [38] 0 0
Canada
State/province [38] 0 0
New Brunswick
Country [39] 0 0
Canada
State/province [39] 0 0
Newfoundland and Labrador
Country [40] 0 0
Canada
State/province [40] 0 0
Nova Scotia
Country [41] 0 0
Canada
State/province [41] 0 0
Ontario
Country [42] 0 0
Canada
State/province [42] 0 0
Quebec
Country [43] 0 0
Canada
State/province [43] 0 0
Saskatchewan
Country [44] 0 0
New Zealand
State/province [44] 0 0
Auckland
Country [45] 0 0
New Zealand
State/province [45] 0 0
Dunedin
Country [46] 0 0
New Zealand
State/province [46] 0 0
Riccarton
Country [47] 0 0
New Zealand
State/province [47] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT00101686
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00101686