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Modified Bolus 5-FU/LV with Irinotecan

Phase 3

Colorectal Neoplasms | Small molecule | Oncology |Pfizer, Inc.|Last Updated: Jan 12, 2010

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedCONTROLLEDDMCBiomarker
Total Trials1
Total Enrollment547
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT00101686Trial Of Irinotecan In Combination With Three Methods Of Administration Of Fluoropyrimidine.PHASE3 COMPLETED 547Feb 1, 2003Oct 1, 2008Jan 12, 2010175 United States, Australia +2
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Study Endpoints
Primary Endpoints
Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL
every 6 weeks until disease progression

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).

Secondary Endpoints
Time to Progression: FOLFIRI, mIFL and CapeIRI
every 6 weeks until disease progression
Overall Response: FOLFIRI, mIFL and CapeIRI
every 6 weeks during chemotherapy until disease progression
Survival Time: FOLFIRI, mIFL and CapeIRI
assessed at least every week during treatment and at least every 3 months during follow-up
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Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Modified Bolus 5-FU/LV with IrinotecanEXPERIMENTAL -
FOLFIRI + bevacizumabEXPERIMENTAL -
miFL + bevacizumabEXPERIMENTAL -
Infusional 5-FU/LV with IrinotecanEXPERIMENTAL -
Oral Capecitabine with IrinotecanOTHER -
Interventions
NameTypeDescription
Modified Bolus 5-FU/LV with IrinotecanDRUGDay 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 + bevacizumabDRUGDay 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 + bevacizumabDRUGDay 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 IrinotecanDRUGDay 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 IrinotecanDRUGDay 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).
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites175

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 be...

Countries:United StatesAustraliaCanadaNew Zealand
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