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

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00101686
First received: January 12, 2005
Last updated: January 4, 2010
Last verified: January 2010
  Purpose

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.


Condition Intervention Phase
Colorectal Neoplasms
Drug: Modified Bolus 5-FU/LV with Irinotecan
Drug: FOLFIRI + bevacizumab
Drug: miFL + bevacizumab
Drug: Infusional 5-FU/LV with Irinotecan
Drug: Oral Capecitabine with Irinotecan
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Time to Progression (TTP) at Primary Completion: FOLFIRI and mIFL [ Time Frame: every 6 weeks until disease progression ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to Progression: FOLFIRI, mIFL and CapeIRI [ Time Frame: every 6 weeks until disease progression ] [ Designated as safety issue: No ]
  • Overall Response: FOLFIRI, mIFL and CapeIRI [ Time Frame: every 6 weeks during chemotherapy until disease progression ] [ Designated as safety issue: No ]
  • Survival Time: FOLFIRI, mIFL and CapeIRI [ Time Frame: assessed at least every week during treatment and at least every 3 months during follow-up ] [ Designated as safety issue: No ]
  • 1 Year Survival: FOLFIRI, mIFL and CapeIRI [ Time Frame: 1 year from date of randomization ] [ Designated as safety issue: No ]
  • Time to Progression : Celecoxib and Placebo [ Time Frame: every 6 weeks until disease progression ] [ Designated as safety issue: No ]
  • Overall Response: Celecoxib and Placebo [ Time Frame: every 6 weeks during chemotherapy until disease progression ] [ Designated as safety issue: No ]
  • Survival Time: Celecoxib and Placebo [ Time Frame: assessed at least every week during treatment and at least every 3 months during follow-up ] [ Designated as safety issue: No ]
  • Time to Progression: Bevacizumab With FOLFIRI, mIFL [ Time Frame: every 6 weeks until disease progression ] [ Designated as safety issue: No ]
  • Overall Response: Bevacizumab With FOLFIRI, mIFL [ Time Frame: every 6 weeks during chemotherapy until disease progression ] [ Designated as safety issue: No ]
  • 1 Year Survival: Bevacizumab With FOLFIRI, mIFL [ Time Frame: 1 year from date of randomization ] [ Designated as safety issue: No ]
  • Survival Time at Last Follow-Up Visit: Bevacizumab With FOLFIRI, mIFL [ Time Frame: Last Follow-Up Visit ] [ Designated as safety issue: No ]
  • Dose Reduction Due to Treatment Emergent Adverse Events [ Time Frame: Day 1; Day 8; and at end of every 3 treatment cycles for FOLFIRI; end of every 2 cycles for mIRI ] [ Designated as safety issue: No ]
  • Overall Relative Dose Intensity of Irinotecan [ Time Frame: End of treatment cycle ] [ Designated as safety issue: No ]

Enrollment: 547
Study Start Date: February 2003
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Modified Bolus 5-FU/LV with Irinotecan 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).
Experimental: FOLFIRI + bevacizumab 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

Experimental: miFL + bevacizumab 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
Experimental: Infusional 5-FU/LV with Irinotecan 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).
Oral Capecitabine with Irinotecan 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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00101686

  Show 175 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier: NCT00101686     History of Changes
Other Study ID Numbers: CPTAIV-0020-411, A5961021
Study First Received: January 12, 2005
Results First Received: October 20, 2009
Last Updated: January 4, 2010
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Capecitabine
Irinotecan
Bevacizumab
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Angiogenesis Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014