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

NCT00101686 | Completed Phase 3 Results DMC

• 2 other identifiers: CPTAIV-0020-411A5961021
• Study Type: interventional
• Target: 547
• Locations: 4 countries
• Sites: 175

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.

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• 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

• 1 Year Survival: FOLFIRI, mIFL and CapeIRI

  1 year from date of randomization

• Time to Progression : Celecoxib and Placebo

  every 6 weeks until disease progression

Study Arms (5)

Modified Bolus 5-FU/LV with Irinotecan

EXPERIMENTAL

Drug: Modified Bolus 5-FU/LV with Irinotecan

FOLFIRI + bevacizumab

EXPERIMENTAL

Drug: FOLFIRI + bevacizumab

miFL + bevacizumab

EXPERIMENTAL

Drug: miFL + bevacizumab

Infusional 5-FU/LV with Irinotecan

EXPERIMENTAL

Drug: Infusional 5-FU/LV with Irinotecan

Oral Capecitabine with Irinotecan

OTHER

Drug: Oral Capecitabine with Irinotecan

Interventions

Modified Bolus 5-FU/LV with Irinotecan 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).

Modified Bolus 5-FU/LV with Irinotecan

FOLFIRI + bevacizumab 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

FOLFIRI + bevacizumab

miFL + bevacizumab 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

miFL + bevacizumab

Infusional 5-FU/LV with Irinotecan 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).

Infusional 5-FU/LV with Irinotecan

Oral Capecitabine with Irinotecan 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).

Oral Capecitabine with Irinotecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (175)

Pfizer Investigational Site

Birmgingham, Alabama, 35205, United States

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Birmingham, Alabama, 35205, United States

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Birmngham, Alabama, 35211, United States

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Mobile, Alabama, 36608, United States

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Flagstaff, Arizona, 86001, United States

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Sedona, Arizona, 86336, United States

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Tucson, Arizona, 85712, United States

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Hot Spring, Arkansas, 71913, United States

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Springdale, Arkansas, 72764, United States

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Arroyo Grande, California, 93420, United States

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Fountian Valley, California, 92708, United States

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Fresno, California, 93710, United States

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Los Gatos, California, 95032, United States

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Mission Hills, California, 91345, United States

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Modesto, California, 95355, United States

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Orange, California, 92868, United States

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Oxnard, California, 93030, United States

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San Diego, California, 92123, United States

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San Jose, California, 95125, United States

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Boulder, Colorado, 80304, United States

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Norwalk, Connecticut, 06581, United States

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Stamford, Connecticut, 06902-3628, United States

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Washington D.C., District of Columbia, 20007, United States

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Altamonte Springs, Florida, 32701, United States

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Hollywood, Florida, 33021, United States

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Lauderhill, Florida, 33319, United States

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Miami, Florida, 33133, United States

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Miami Beach, Florida, United States

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New Port Richey, Florida, 34652, United States

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Ocala, Florida, 34474, United States

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Sarasota, Florida, 34239, United States

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Tamarac, Florida, 33321, United States

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Macon, Georgia, 31201, United States

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Niles, Illinois, 60714, United States

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Rockford, Illinois, 61108-2472, United States

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Skokie, Illinois, 60077, United States

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Fishers, Indiana, 46038, United States

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Fort Wayne, Indiana, 46815, United States

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Terre Haute, Indiana, 47802, United States

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Overland Park, Kansas, 66210, United States

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Alexandria, Louisiana, 71301, United States

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Shrevport, Louisiana, 71101, United States

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Bangor, Maine, 04401, United States

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Annapolis, Maryland, 21401, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02115, United States

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Boston, Massachusetts, 02215, United States

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Burlington, Massachusetts, 01805, United States

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Pittsfield, Massachusetts, 01201, United States

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Grand Rapids, Michigan, 49603, United States

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Burnsville, Minnesota, 55337, United States

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Robbinsdale, Minnesota, 55422, United States

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Columbia, Missouri, 65201, United States

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Columbia, Missouri, 65203, United States

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Joplin, Missouri, 64804, United States

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St Louis, Missouri, 63136, United States

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St Louis, Missouri, 63141, United States

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Billings, Montana, 59101, United States

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Omaha, Nebraska, 68131, United States

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Las Vegas, Nevada, 89109, United States

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Hooksett, New Hampshire, 03106, United States

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Lebanon, New Hampshire, 03756-0001, United States

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Nashua, New Hampshire, 03060, United States

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Summit, New Jersey, 07901, United States

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Albuquerque, New Mexico, 87109, United States

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Farmington, New Mexico, 87401, United States

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Santa Fe, New Mexico, 87501, United States

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Albany, New York, 12208, United States

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Manhaset, New York, 11030, United States

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Rockville Centre, New York, 11570, United States

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Asheville, North Carolina, 28801, United States

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Cary, North Carolina, 27511, United States

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Fayetteville, North Carolina, 28302-2000, United States

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Greensboro, North Carolina, 27403, United States

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Hendersonville, North Carolina, 28791, United States

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Hickory, North Carolina, 28602, United States

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Winston-Salem, North Carolina, 27103, United States

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Winston-Salem, North Carolina, 27157, United States

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Columbus, Ohio, 43215, United States

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Dayton, Ohio, 45409, United States

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Bartlesville, Oklahoma, 74006, United States

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Norman, Oklahoma, 73071, United States

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Oklahoma City, Oklahoma, 73104, United States

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Eugene, Oregon, 97401, United States

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Portland, Oregon, 97213, United States

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Abington, Pennsylvania, 19001, United States

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Philadelphia, Pennsylvania, 19014-4283, United States

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Philadelphia, Pennsylvania, 19107, United States

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Philadelphia, Pennsylvania, 19141, United States

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Reading, Pennsylvania, 19603, United States

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Chattanooga, Tennessee, 37404, United States

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Collierville, Tennessee, 38017, United States

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Germantown, Tennessee, 38138, United States

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Jackson, Tennessee, 38301, United States

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Knoxville, Tennessee, 37916, United States

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Knoxville, Tennessee, 37920, United States

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Abilene, Texas, 79606-5208, United States

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Arlington, Texas, 76012, United States

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Austin, Texas, 78705, United States

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Austin, Texas, 78731, United States

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Beaumont, Texas, 77702-1449, United States

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Bedford, Texas, 76022, United States

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Dallas, Texas, 75230-2510, United States

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Dallas, Texas, 75231-4400, United States

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Dallas, Texas, 75237, United States

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Dallas, Texas, 75246, United States

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Denton, Texas, 76210, United States

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El Paso, Texas, 79902, United States

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El Paso, Texas, 79915, United States

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Fort Worth, Texas, 76104, United States

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Fredericksburg, Texas, 78624-3847, United States

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Garland, Texas, 75042, United States

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Houston, Texas, 77030, United States

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Houston, Texas, 77054, United States

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Irving, Texas, 75061-224, United States

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Lewisville, Texas, 75067, United States

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Longview, Texas, 75601, United States

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McAllen, Texas, 78503, United States

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Mesquite, Texas, 75050, United States

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Midland, Texas, 79701, United States

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New Braunfels, Texas, 78130, United States

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Odessa, Texas, 79761, United States

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Paris, Texas, 75460, United States

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Sherman, Texas, 75090-0504, United States

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Temple, Texas, 76508, United States

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Tyler, Texas, 75701-2001, United States

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Tyler, Texas, 75702, United States

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Waco, Texas, 76712, United States

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Webster, Texas, 77598, United States

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Wichita Falls, Texas, 76310, United States

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Colchester, Vermont, 05446, United States

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Fairfax, Virginia, 22031, United States

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Newport News, Virginia, 23606, United States

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Roanoke, Virginia, 24014, United States

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Edmonds, Washington, 98026, United States

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Lacy, Washington, 98503, United States

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Seattle, Washington, 98133, United States

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Spokane, Washington, 99202, United States

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Yakima, Washington, 98902, United States

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Glendale, Wisconsin, 53212, United States

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Milwaukee, Wisconsin, 53226, United States

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Waratah, New South Wales, 2298, Australia

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South Brisbane, Queensland, 4101, Australia

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Bedford Park, South Australia, 5042, Australia

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Woodville, South Australia, 5011, Australia

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Clayton, Victoria, 3168, Australia

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Frankston, Victoria, 3199, Australia

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Moncton, New Brunswick, E1C 8X3, Canada

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St. John's, Newfoundland and Labrador, A1B 3V76, Canada

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Halifax, Nova Scotia, B3H 2Y9, Canada

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Sydney, Nova Scotia, B1P 1P3, Canada

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Brampton, Ontario, L6W 3X4, Canada

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Kingston, Ontario, K7L 5P9, Canada

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Kitchener, Ontario, N2G 1G3, Canada

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Mississauga, Ontario, L5B 1B8, Canada

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Newmarket, Ontario, L3Y 2P9, Canada

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Oshawa, Ontario, L1G 2B9, Canada

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Ottawa, Ontario, K1H 1C4, Canada

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Scarborough Village, Ontario, M1P 2V5, Canada

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Thunder Bay, Ontario, P7A 7T1, Canada

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Windsor, Ontario, N8W 2X3, Canada

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Chicoutimi, Quebec, G7H 5H6, Canada

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Fleurimont, Quebec, J1H 5N4, Canada

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Laval, Quebec, H7M 3L9, Canada

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Montreal, Quebec, H1T 4B3, Canada

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Montreal, Quebec, H2W 1S6, Canada

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Montreal, Quebec, H2X 3J4, Canada

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Québec, Quebec, Canada

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Rimouski, Quebec, G5L 5T1, Canada

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Regina, Saskatchewan, S4T 7T1, Canada

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Saskatoon, Saskatchewan, S7N 4H4, Canada

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Auckland, 1, New Zealand

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Dunedin, 9001, New Zealand

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Riccarton, 8020, New Zealand

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Wellington, 6039, New Zealand

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MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; Bevacizumab; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.govCallCenter@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 12, 2005
• First Posted: January 13, 2005
• Study Start: February 1, 2003
• Primary Completion: October 1, 2008
• Study Completion: October 1, 2008
• Last Updated: January 12, 2010
• Results First Posted: November 26, 2009

Record last verified: 2010-01

Locations

AU (6); US (141); NZ (4); CA (24)