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

NCT ID: NCT00101686

Last Updated: 2010-01-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

547 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-02-28

Study Completion Date

2008-10-31

Brief Summary

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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.

Detailed Description

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Conditions

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Colorectal Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Modified Bolus 5-FU/LV with Irinotecan

Group Type EXPERIMENTAL

Modified Bolus 5-FU/LV with Irinotecan

Intervention Type DRUG

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

Group Type EXPERIMENTAL

FOLFIRI + bevacizumab

Intervention Type DRUG

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

Group Type EXPERIMENTAL

miFL + bevacizumab

Intervention Type DRUG

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

Group Type EXPERIMENTAL

Infusional 5-FU/LV with Irinotecan

Intervention Type DRUG

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

Group Type OTHER

Oral Capecitabine with Irinotecan

Intervention Type DRUG

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).

Interventions

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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).

Intervention Type 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

Intervention Type 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

Intervention Type 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).

Intervention Type 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).

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Pfizer Inc

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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Birmgingham, Alabama, United States

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Birmingham, Alabama, United States

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Birmngham, Alabama, United States

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Mobile, Alabama, United States

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Flagstaff, Arizona, United States

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Sedona, Arizona, United States

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Tucson, Arizona, United States

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Hot Spring, Arkansas, United States

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Springdale, Arkansas, United States

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Arroyo Grande, California, United States

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Fountian Valley, California, United States

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Fresno, California, United States

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Los Gatos, California, United States

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Mission Hills, California, United States

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Modesto, California, United States

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Orange, California, United States

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Oxnard, California, United States

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San Diego, California, United States

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San Jose, California, United States

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Boulder, Colorado, United States

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Norwalk, Connecticut, United States

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Stamford, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Altamonte Springs, Florida, United States

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Hollywood, Florida, United States

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Lauderhill, Florida, United States

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Miami, Florida, United States

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Miami Beach, Florida, United States

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New Port Richey, Florida, United States

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Ocala, Florida, United States

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Tamarac, Florida, United States

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Temple, Texas, United States

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Webster, Texas, United States

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Fairfax, Virginia, United States

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Newport News, Virginia, United States

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Roanoke, Virginia, United States

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Edmonds, Washington, United States

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Lacy, Washington, United States

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Seattle, Washington, United States

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Spokane, Washington, United States

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Yakima, Washington, United States

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Glendale, Wisconsin, United States

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Milwaukee, Wisconsin, United States

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Waratah, New South Wales, Australia

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South Brisbane, Queensland, Australia

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Bedford Park, South Australia, Australia

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Woodville, South Australia, Australia

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Clayton, Victoria, Australia

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Frankston, Victoria, Australia

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Moncton, New Brunswick, Canada

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St. John's, Newfoundland and Labrador, Canada

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Halifax, Nova Scotia, Canada

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Sydney, Nova Scotia, Canada

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Brampton, Ontario, Canada

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Kingston, Ontario, Canada

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Kitchener, Ontario, Canada

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Mississauga, Ontario, Canada

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Newmarket, Ontario, Canada

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Oshawa, Ontario, Canada

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Ottawa, Ontario, Canada

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Scarborough Village, Ontario, Canada

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Thunder Bay, Ontario, Canada

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Windsor, Ontario, Canada

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Chicoutimi, Quebec, Canada

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Fleurimont, Quebec, Canada

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Laval, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Rimouski, Quebec, Canada

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Regina, Saskatchewan, Canada

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Saskatoon, Saskatchewan, Canada

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Auckland, , New Zealand

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Dunedin, , New Zealand

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Riccarton, , New Zealand

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Wellington, , New Zealand

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Countries

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United States Australia Canada New Zealand

Other Identifiers

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A5961021

Identifier Type: -

Identifier Source: secondary_id

CPTAIV-0020-411

Identifier Type: -

Identifier Source: org_study_id

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