A Study Combining FOLFOX or FOLFIRI With AG-013736 or Bevacizumab (Avastin) in Patients With Metastatic Colorectal Cancer After Failure Of One First Line Regimen

A Randomized, Phase 2 Study Of FOLFOX Or FOLFIRI With AG-013736 Or Bevacizumab (Avastin) In Patients With Metastatic Colorectal Cancer After Failure Of An Irinotecan Or Oxaliplatin-Containing First-Line Regimen

The study is designed to demonstrate that the combination of AG-013736 with either FOLFIRI or FOLFOX is superior to FOLFIRI or FOLFOX in combination with bevacizumab (Avastin) in delaying tumor progression in the second-line treatment of patients with metastatic colorectal cancer after failure of an irinotecan or oxaliplatin-containing first-line regimen.

Study Overview

• Status: Completed
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: Bevacizumab (avastin); Drug: FOLFIRI (Irinotecan, leucovorin, 5-fluorouracil [5FU]); Drug: Bevacizumab (avastin); Drug: AG-013736 (axitinib); Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]); Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]); Drug: FOLFIRI (irinotecan, leucovorin, 5-fluorouracil [5FU])

• Study Type: Interventional
• Enrollment (Actual): 171
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Pfizer Investigational Site
    • Levis, Quebec, Canada, G6V 3Z1
      • Pfizer Investigational Site
    • Montreal, Quebec, Canada, H2X 3J4
      • Pfizer Investigational Site
• France
  • Lille, France, 59020
    • Pfizer Investigational Site
  • Montpellier, France, 34094
    • Pfizer Investigational Site
  • Paris, France, 75012
    • Pfizer Investigational Site
  • Villejuif, France, 94805
    • Pfizer Investigational Site
• Italy
  • Genova, Italy, 16132
    • Pfizer Investigational Site
  • Padova, Italy, 35128
    • Pfizer Investigational Site
  • Roma, Italy, 00168
    • Pfizer Investigational Site
  • Roma, Italy, 00152
    • Pfizer Investigational Site
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan
      • Pfizer Investigational Site
  • Shizuoka
    • Suntougun, Shizuoka, Japan
      • Pfizer Investigational Site
  • Tokyo
    • Chuo-ku, Tokyo, Japan
      • Pfizer Investigational Site
• Korea, Republic of
  • Daegu, Korea, Republic of, 700-721
    • Pfizer Investigational Site
  • Jeollanam-do, Korea, Republic of, 519-809
    • Pfizer Investigational Site
  • Seoul, Korea, Republic of, 139-706
    • Pfizer Investigational Site
• Poland
  • Warszawa, Poland, 02-781
    • Pfizer Investigational Site
  • Warszawa, Poland, 02-097
    • Pfizer Investigational Site
• Spain
  • Madrid, Spain, 28033
    • Pfizer Investigational Site
  • Barcelona
    • L'hospitalet de Llobregat, Barcelona, Spain, 08907
      • Pfizer Investigational Site
    • Sabadell, Barcelona, Spain, 08208
      • Pfizer Investigational Site
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Pfizer Investigational Site
  • California
    • Antioch, California, United States, 94531
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90095
      • Pfizer Investigational Site
    • Los Angeles, California, United States, 90095-6984
      • Pfizer Investigational Site
    • Pleasant Hill, California, United States, 94523
      • Pfizer Investigational Site
    • San Leandro, California, United States, 94578
      • Pfizer Investigational Site
    • Santa Monica, California, United States, 90404
      • Pfizer Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Pfizer Investigational Site
  • Florida
    • Bonita Springs, Florida, United States, 34135
      • Pfizer Investigational Site
    • Bradenton, Florida, United States, 34209
      • Pfizer Investigational Site
    • Cape Coral, Florida, United States, 33990
      • Pfizer Investigational Site
    • Cape Coral, Florida, United States, 33914
      • Pfizer Investigational Site
    • Englewood, Florida, United States, 34223
      • Pfizer Investigational Site
    • Fort Myers, Florida, United States, 33916
      • Pfizer Investigational Site
    • Fort Myers, Florida, United States, 33901-8108
      • Pfizer Investigational Site
    • Fort Myers, Florida, United States, 33905
      • Pfizer Investigational Site
    • Fort Myers, Florida, United States, 33908
      • Pfizer Investigational Site
    • Naples, Florida, United States, 34102
      • Pfizer Investigational Site
    • Naples, Florida, United States, 34119
      • Pfizer Investigational Site
    • Port Charlotte, Florida, United States, 33980
      • Pfizer Investigational Site
    • Sarasota, Florida, United States, 34232
      • Pfizer Investigational Site
    • Sarasota, Florida, United States, 34236
      • Pfizer Investigational Site
    • Venice, Florida, United States, 34285
      • Pfizer Investigational Site
    • Venice, Florida, United States, 34292
      • Pfizer Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Pfizer Investigational Site
    • Ringgold, Georgia, United States, 30736
      • Pfizer Investigational Site
  • Iowa
    • Dubuque, Iowa, United States, 52001
      • Pfizer Investigational Site
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • Pfizer Investigational Site
    • Paducah, Kentucky, United States, 42002
      • Pfizer Investigational Site
    • Paducah, Kentucky, United States, 42003
      • Pfizer Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Pfizer Investigational Site
  • Mississippi
    • New Albany, Mississippi, United States, 38652
      • Pfizer Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45219
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45230
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45236
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45238
      • Pfizer Investigational Site
    • Cincinnati, Ohio, United States, 45248
      • Pfizer Investigational Site
    • Fairfield, Ohio, United States, 45014
      • Pfizer Investigational Site
    • Hamilton, Ohio, United States, 45013
      • Pfizer Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Pfizer Investigational Site
    • Franklin, Tennessee, United States, 37067
      • Pfizer Investigational Site
    • Gallatin, Tennessee, United States, 37066
      • Pfizer Investigational Site
    • Germantown, Tennessee, United States, 38138
      • Pfizer Investigational Site
    • Hermitage, Tennessee, United States, 37076
      • Pfizer Investigational Site
    • Hixson, Tennessee, United States, 37343
      • Pfizer Investigational Site
    • Lebanon, Tennessee, United States, 37087
      • Pfizer Investigational Site
    • Murfreesboro, Tennessee, United States, 37130
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37203
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37232
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37205
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37207
      • Pfizer Investigational Site
    • Nashville, Tennessee, United States, 37211
      • Pfizer Investigational Site
    • Paris, Tennessee, United States, 38242
      • Pfizer Investigational Site
    • Smyrna, Tennessee, United States, 37167
      • Pfizer Investigational Site
    • Union City, Tennessee, United States, 38261
      • Pfizer Investigational Site
  • Texas
    • Corpus Christi, Texas, United States, 78463
      • Pfizer Investigational Site
  • Virginia
    • Mechanicsville, Virginia, United States, 23116
      • Pfizer Investigational Site
    • Midlothian, Virginia, United States, 23114
      • Pfizer Investigational Site
    • Richmond, Virginia, United States, 23235
      • Pfizer Investigational Site
    • Richmond, Virginia, United States, 23230
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically documented colorectal cancer plus one of the following:
• Failure of one prior irinotecan- or oxaliplatin-containing regimen, or
• Adjuvant refractory to irinotecan- or oxaliplatin-containing regimen.

Exclusion Criteria:

• Prior treatment in first line metastatic setting with more than one regimen
• Prior irradiation of more than 25% of bone marrow.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: B; Bevacizumab (avastin)	Drug: Bevacizumab (avastin); Bevacizumab intravenous [IV] infusion 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.; Drug: FOLFIRI (Irinotecan, leucovorin, 5-fluorouracil [5FU]); Irinotecan (180 mg/m²) intravenous infusion [IV] over 90 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed immediately by 5-FU bolus (400 mg/m²) intravenous [IV] and a subsequent 5-FU infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.; Drug: Bevacizumab (avastin); Bevacizumab intravenous infusion [IV] 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.
Experimental: C; AG-013736 (axitinib)	Drug: AG-013736 (axitinib); Axitinib is given at a starting dose of 5 mg twice daily [BID] continuous dosing until disease progression, intolerance or withdrawal of consent.; Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]); Oxaliplatin (85 mg/m²) intravenous infusion [IV] over 120 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed by 5-FU IV bolus (400 mg/m²) and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.; Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]); Oxaliplatin (85 mg/m²) IV infusion over 120 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed by 5-FU IV bolus (400 mg/m²) and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.
Experimental: A; AG-013736 (axitinib)	Drug: AG-013736 (axitinib); Axitinib is given at a starting dose of 5 mg twice daily [BID] continuous dosing until disease progression, intolerance or withdrawal of consent.; Drug: FOLFIRI (irinotecan, leucovorin, 5-fluorouracil [5FU]); Irinotecan (180 mg/m²) intravenous infusion [IV] over 90 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed immediately by 5-FU bolus (400 mg/m²) IV and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.
Active Comparator: D; bevacizumab (avastin)	Drug: Bevacizumab (avastin); Bevacizumab intravenous [IV] infusion 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.; Drug: Bevacizumab (avastin); Bevacizumab intravenous infusion [IV] 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.; Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]); Oxaliplatin (85 mg/m²) intravenous infusion [IV] over 120 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed by 5-FU IV bolus (400 mg/m²) and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.; Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]); Oxaliplatin (85 mg/m²) IV infusion over 120 minutes, concurrently with leucovorin (400 mg/m²) intravenous infusion [IV] over 2 hours followed by 5-FU IV bolus (400 mg/m²) and a subsequent 5-FU IV infusion (2400 mg/m² over 46-48 hours), repeated every 2 weeks until disease progression, intolerance or withdrawal of consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").	Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 week up to 130 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death).	Baseline until death or up to 1 year after the randomization of last participant
Percentage of Participants With Objective Response (OR)	Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. PR are those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.	Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks
Duration of Response (DR)	Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response.	Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks
Change From Baseline in MD Anderson Symptoms Inventory Diarrhea (MDASI-D) Symptom Severity Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal	Symptom severity score is comprised of average of 14 MDASI-D core items (pain, fatigue, nausea, disturbed sleep, distress, shortness of breath, remembering things, lack of appetite, drowsiness, dry mouth, sadness, vomiting, numbness or tingling and diarrhea) and ranges from 0 to 10. Participants were asked to rate severity of each symptom at their worst in last week; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Lower scores indicated better outcome. Total average score range: 0 to 10.	Baseline, Day 1 of cycles 2- 5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal
Change From Baseline in MDASI-D Symptom Interference Score at Day 1 of Cycles 2-5, Day 1 of Every Odd-numbered Cycle Throughout the Study and End of Treatment (Cycle 65) or Withdrawal	Symptom Interference score is comprised of the average of 6 items on feeling or function from the MDASI-D core (general activity, mood, work, relations with others, walking, and enjoyment of life) and ranges from 0 to 10. Participants were asked to rate how much symptoms have interfered in last week; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Lower scores indicated better outcome. Total average score range: 0 to 10.	Baseline, Day 1 of cycle 2-5, Day 1 of every odd-numbered cycle throughout the study and end of treatment (cycle 65) or withdrawal

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 1, 2008
• First Submitted That Met QC Criteria: February 1, 2008
• First Posted (Estimate): February 14, 2008

Study Record Updates

• Last Update Posted (Estimate): April 19, 2013
• Last Update Submitted That Met QC Criteria: April 12, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Protein Kinase Inhibitors; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Bevacizumab; Leucovorin; Irinotecan; Levoleucovorin; Axitinib
• Other Study ID Numbers: A4061034