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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00615056
First received: February 1, 2008
Last updated: April 12, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Colorectal Neoplasms
Drug: Bevacizumab (avastin)
Drug: FOLFIRI (Irinotecan, leucovorin, 5-fluorouracil [5FU])
Drug: AG-013736 (axitinib)
Drug: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])
Drug: FOLFIRI (irinotecan, leucovorin, 5-fluorouracil [5FU])
Phase 2

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, 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 week up to 130 weeks ] [ Designated as safety issue: No ]
    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").


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Baseline until death or up to 1 year after the randomization of last participant ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants With Objective Response (OR) [ Time Frame: Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks ] [ Designated as safety issue: No ]
    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.

  • Duration of Response (DR) [ Time Frame: Baseline until disease progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 130 weeks ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 171
Study Start Date: March 2008
Study Completion Date: April 2012
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
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 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) 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.

  Eligibility

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

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.
  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: NCT00615056

  Show 83 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00615056     History of Changes
Other Study ID Numbers: A4061034
Study First Received: February 1, 2008
Results First Received: March 28, 2012
Last Updated: April 12, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Axitinib
Bevacizumab
Camptothecin
Fluorouracil
Irinotecan
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 21, 2014