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

Colorectal Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00615056
• Other study ID #: A4061034
• Status: Completed
• Phase: Phase 2
• First received: February 1, 2008
• Last updated: April 12, 2013
• Start date: March 2008
• Est. completion date: April 2012

Study information

• Verified date: April 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 171
• Est. completion date: April 2012
• Est. primary completion date: March 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Colorectal Neoplasms

Intervention

Drug:
• Bevacizumab (avastin)
Bevacizumab intravenous [IV] infusion 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.
• 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.
• 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.
• 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.
• 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.
• 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.
• Bevacizumab (avastin)
Bevacizumab intravenous infusion [IV] 5 mg/kg every two weeks until disease progression, intolerance or withdrawal of consent.
• 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.

Locations

Country	Name	City	State
Canada	Pfizer Investigational Site	Greenfield Park	Quebec
Canada	Pfizer Investigational Site	Levis	Quebec
Canada	Pfizer Investigational Site	Montreal	Quebec
France	Pfizer Investigational Site	Lille
France	Pfizer Investigational Site	Montpellier
France	Pfizer Investigational Site	Paris
France	Pfizer Investigational Site	Villejuif
Italy	Pfizer Investigational Site	Genova
Italy	Pfizer Investigational Site	Padova
Italy	Pfizer Investigational Site	Roma
Italy	Pfizer Investigational Site	Roma
Japan	Pfizer Investigational Site	Chuo-ku	Tokyo
Japan	Pfizer Investigational Site	Kashiwa	Chiba
Japan	Pfizer Investigational Site	Suntougun	Shizuoka
Korea, Republic of	Pfizer Investigational Site	Daegu
Korea, Republic of	Pfizer Investigational Site	Jeollanam-do
Korea, Republic of	Pfizer Investigational Site	Seoul
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Warszawa
Spain	Pfizer Investigational Site	L'hospitalet de Llobregat	Barcelona
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Sabadell	Barcelona
United States	Pfizer Investigational Site	Antioch	California
United States	Pfizer Investigational Site	Atlanta	Georgia
United States	Pfizer Investigational Site	Aurora	Colorado
United States	Pfizer Investigational Site	Baltimore	Maryland
United States	Pfizer Investigational Site	Bonita Springs	Florida
United States	Pfizer Investigational Site	Bradenton	Florida
United States	Pfizer Investigational Site	Cape Coral	Florida
United States	Pfizer Investigational Site	Cape Coral	Florida
United States	Pfizer Investigational Site	Chattanooga	Tennessee
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Cincinnati	Ohio
United States	Pfizer Investigational Site	Corpus Christi	Texas
United States	Pfizer Investigational Site	Crestview Hills	Kentucky
United States	Pfizer Investigational Site	Dubuque	Iowa
United States	Pfizer Investigational Site	Englewood	Florida
United States	Pfizer Investigational Site	Fairfield	Ohio
United States	Pfizer Investigational Site	Fort Myers	Florida
United States	Pfizer Investigational Site	Fort Myers	Florida
United States	Pfizer Investigational Site	Fort Myers	Florida
United States	Pfizer Investigational Site	Fort Myers	Florida
United States	Pfizer Investigational Site	Franklin	Tennessee
United States	Pfizer Investigational Site	Gallatin	Tennessee
United States	Pfizer Investigational Site	Germantown	Tennessee
United States	Pfizer Investigational Site	Hamilton	Ohio
United States	Pfizer Investigational Site	Hermitage	Tennessee
United States	Pfizer Investigational Site	Hixson	Tennessee
United States	Pfizer Investigational Site	Lebanon	Tennessee
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Los Angeles	California
United States	Pfizer Investigational Site	Mechanicsville	Virginia
United States	Pfizer Investigational Site	Midlothian	Virginia
United States	Pfizer Investigational Site	Mobile	Alabama
United States	Pfizer Investigational Site	Murfreesboro	Tennessee
United States	Pfizer Investigational Site	Naples	Florida
United States	Pfizer Investigational Site	Naples	Florida
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	Nashville	Tennessee
United States	Pfizer Investigational Site	New Albany	Mississippi
United States	Pfizer Investigational Site	Paducah	Kentucky
United States	Pfizer Investigational Site	Paducah	Kentucky
United States	Pfizer Investigational Site	Paris	Tennessee
United States	Pfizer Investigational Site	Pleasant Hill	California
United States	Pfizer Investigational Site	Port Charlotte	Florida
United States	Pfizer Investigational Site	Richmond	Virginia
United States	Pfizer Investigational Site	Richmond	Virginia
United States	Pfizer Investigational Site	Ringgold	Georgia
United States	Pfizer Investigational Site	San Leandro	California
United States	Pfizer Investigational Site	Santa Monica	California
United States	Pfizer Investigational Site	Sarasota	Florida
United States	Pfizer Investigational Site	Sarasota	Florida
United States	Pfizer Investigational Site	Smyrna	Tennessee
United States	Pfizer Investigational Site	Union City	Tennessee
United States	Pfizer Investigational Site	Venice	Florida
United States	Pfizer Investigational Site	Venice	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada,  France,  Italy,  Japan,  Korea, Republic of,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

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