Phase 2 Study of ABT-869 in Combination With mFOLFOX6 Versus Bevacizumab in Combination With mFOLFOX6 to Treat Advanced Colorectal Cancer

May 7, 2013 updated by: AbbVie (prior sponsor, Abbott)

An Open-Label, Randomized Phase 2 Study of ABT-869 in Combination With mFOLFOX6 (Oxaliplatin, 5-Fluorouracil, and Folinic Acid) Versus Bevacizumab in Combination With mFOLFOX6 as Second-line Treatment of Subjects With Advanced Colorectal Cancer

To determine the effect of ABT-869 plus mFOLFOX6 compared to bevacizumab plus mFOLFOX6 on disease progression in advanced colorectal cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

159

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Bedford Park, Australia, 5042
        • Site Reference ID/Investigator# 18581
      • Herston, Australia, 4029
        • Site Reference ID/Investigator# 23443
  • Belgium
      • Bonheiden, Belgium, 2820
        • Site Reference ID/Investigator# 18023
      • Brussels, Belgium, 1200
        • Site Reference ID/Investigator# 23646
      • Leuven, Belgium, 3000
        • Site Reference ID/Investigator# 18026
      • Roeselare, Belgium, 8800
        • Site Reference ID/Investigator# 18022
  • Brazil
      • Jau, Brazil, 17210-120
        • Site Reference ID/Investigator# 26662
      • Porto Alegre, Brazil, 90610-000
        • Site Reference ID/Investigator# 24245
  • Canada
      • Barrie, Canada, L4M 6M2
        • Site Reference ID/Investigator# 23265
      • Edmonton, Canada, T6G 1Z2
        • Site Reference ID/Investigator# 21083
      • Ottawa, Canada, K1H 8L6
        • Site Reference ID/Investigator# 22465
  • Czech Republic
      • Nachod, Czech Republic, 54769
        • Site Reference ID/Investigator# 22141
  • Greece
      • Heraklion, Greece, 71110
        • Site Reference ID/Investigator# 22289
      • Thessaloniki, Greece, 54007
        • Site Reference ID/Investigator# 22286
      • Thessaloniki, Greece, 56403
        • Site Reference ID/Investigator# 22287
  • Korea, Republic of
      • Seoul, Korea, Republic of, 110-744
        • Site Reference ID/Investigator# 18281
      • Seoul, Korea, Republic of, 135-710
        • Site Reference ID/Investigator# 18283
      • Seoul, Korea, Republic of, 138-736
        • Site Reference ID/Investigator# 18282
  • New Zealand
      • Wellington South, New Zealand, 6021
        • Site Reference ID/Investigator# 20281
  • Poland
      • Olsztyn, Poland, 10513
        • Site Reference ID/Investigator# 20141
      • Warsaw, Poland, 02-781
        • Site Reference ID/Investigator# 17946
      • Warsaw, Poland, 04-125
        • Site Reference ID/Investigator# 38284
  • Portugal
      • Aveiro, Portugal, 3814-501
        • Site Reference ID/Investigator# 23908
      • Coimbra, Portugal, 3001-651
        • Site Reference ID/Investigator# 22324
      • Faro, Portugal, 8000-386
        • Site Reference ID/Investigator# 23724
      • Lisbon, Portugal, 1099-023
        • Site Reference ID/Investigator# 23964
  • Romania
      • Baia Mare, Romania, 430031
        • Site Reference ID/Investigator# 23303
      • Brasov, Romania, 500117
        • Site Reference ID/Investigator# 23302
      • Bucharest, Romania, 022328
        • Site Reference ID/Investigator# 17962
      • Bucharest, Romania, 022328
        • Site Reference ID/Investigator# 17964
      • Bucharest, Romania, 050098
        • Site Reference ID/Investigator# 23304
      • Cluj Napoca, Romania, 400015
        • Site Reference ID/Investigator# 17961
      • Craiova, Romania, 200385
        • Site Reference ID/Investigator# 23305
  • Russian Federation
      • Moscow, Russian Federation, 115478
        • Site Reference ID/Investigator# 24422
      • Moscow, Russian Federation, 115478
        • Site Reference ID/Investigator# 25063
      • Moscow, Russian Federation, 117997
        • Site Reference ID/Investigator# 25065
      • Moscow, Russian Federation, 143423
        • Site Reference ID/Investigator# 24423
  • Spain
      • A Coruna, Spain, 15006
        • Site Reference ID/Investigator# 22809
      • Barcelona, Spain, 08907
        • Site Reference ID/Investigator# 22807
      • Madrid, Spain, 28034
        • Site Reference ID/Investigator# 22804
      • Madrid, Spain, 28050
        • Site Reference ID/Investigator# 22801
      • Pamplona Navarra, Spain, 31008
        • Site Reference ID/Investigator# 22803
      • Santander, Spain, 39008
        • Site Reference ID/Investigator# 22800
  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7305
        • Site Reference ID/Investigator# 11341
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Site Reference ID/Investigator# 20801
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6307
        • Site Reference ID/Investigator# 8360

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

Subject must be >/= 18 years of age. Subject (male or female) must be diagnosed with adenocarcinoma of the colon or rectum. Subject must have metastatic disease or locally recurrent disease that is not amenable to surgical resection with curative intent.

Subject must have received one prior chemotherapy regimen containing irinotecan or a fluoropyrimidine for locally recurrent or metastatic colon or rectal cancer.

Subject has experienced progressive disease during or following the previous anti-tumor treatment.

Subject may have received prior adjuvant treatment for colorectal cancer. Subject has measurable disease by RECIST criteria (randomized portion only). Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1. Subject must have adequate bone marrow, renal and hepatic function. Subject must have Partial Thromboplastin Time (PTT) < 1.5 x Upper Limit of Normal (ULN) and International Normalized Ratio (INR) < 1.5.

Exclusion Criteria:

Subject has received more than one prior therapy in the metastatic setting. Lead-in Cohort only: The subject may have received more than one prior therapy in the metastatic setting.

Subject has received cytotoxic chemotherapy within 21 days prior to Study Day 1.

Subject has received non-cytotoxic, anti-cancer therapy within 21 days or within a period defined by 5 half lives whichever is shorter, prior to Study Day 1.

Subject has not recovered to less than or equal to Grade 1 clinically significant adverse effects/toxicities of the previous therapy.

Subject has received prior treatment with a tyrosine kinase inhibitor targeting VEGF or PDGF.

Subject has received prior treatment with oxaliplatin in the metastatic setting. Lead-in cohort only: Prior treatment with oxaliplatin will be allowed provided that any neuropathy as a result of the oxaliplatin treatment has resolved to less than or equal to Grade 1.

Subject has had major surgery within 28 days of Study Day 1. Subject has had radiotherapy within 14 days of Study Day 1. Subject has a history of hypersensitivity to recombinant murine monoclonal antibodies, oxaliplatin or other platinum-containing compounds, fluorouracil, or folinic acid.

Subject has a known intolerance to bevacizumab. Subject has untreated brain or meningeal metastases. Subject is receiving therapeutic anticoagulation therapy . Subject has a history of/or currently exhibits clinically significant cancer related events of bleeding.

Subject currently exhibits symptomatic or persistent, uncontrolled hypertension.

Subject has a history of myocardial infarction, stroke, or transient ischemic attack within six months of Study Day 1.

History of another active cancer within the past 5 years except cervical cancer in situ, in situ carcinoma of the bladder, squamous cell or basal cell carcinoma of the skin.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: A
Open-label to Bevacizumab plus mFOLFOX6
Drug: bevacizumab
10 mg/kg QD, IV on Day 1 of each 14-day cycle
Drug: oxaliplatin
85 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle
Other Names:
  • mFOLFOX6 regimen
Drug: folinic acid
400 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle
Other Names:
  • mFOLFOX6 regimen
Drug: fluorouracil
400 mg/m2 IV bolus on Day 1 of each 14-day cycle; followed by 2400 mg/m2 IV infusion 46-48 hours
Other Names:
  • mFOLFOX6 regimen
Active Comparator: B
Open-label to High-dose ABT-869 arm plus mFOLFOX6
Drug: oxaliplatin
85 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle
Other Names:
  • mFOLFOX6 regimen
Drug: folinic acid
400 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle
Other Names:
  • mFOLFOX6 regimen
Drug: fluorouracil
400 mg/m2 IV bolus on Day 1 of each 14-day cycle; followed by 2400 mg/m2 IV infusion 46-48 hours
Other Names:
  • mFOLFOX6 regimen
Drug: ABT-869
12.5 mg QD, tablets taken orally days 1-14 of every 14-day cycle
Drug: ABT-869
7.5 mg QD tablets taken orally days 1-14 of every 14-day cycle
Active Comparator: C
Open-label to low-dose ABT-869 arm plus mFOLFOX6
Drug: oxaliplatin
85 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle
Other Names:
  • mFOLFOX6 regimen
Drug: folinic acid
400 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle
Other Names:
  • mFOLFOX6 regimen
Drug: fluorouracil
400 mg/m2 IV bolus on Day 1 of each 14-day cycle; followed by 2400 mg/m2 IV infusion 46-48 hours
Other Names:
  • mFOLFOX6 regimen
Drug: ABT-869
12.5 mg QD, tablets taken orally days 1-14 of every 14-day cycle
Drug: ABT-869
7.5 mg QD tablets taken orally days 1-14 of every 14-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival
Time Frame: Radiographic evaluation every 2 months, clinial evaluation every 2 weeks
Radiographic evaluation every 2 months, clinial evaluation every 2 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: from randomization until patient death or alive at 5 years
from randomization until patient death or alive at 5 years
12-month overall survival rate
Time Frame: from randomization until patient death or alive at 5 years
from randomization until patient death or alive at 5 years
Objective response rate
Time Frame: from randomization until patient death or alive at 5 years
from randomization until patient death or alive at 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AbbVie (prior sponsor, Abbott)

Collaborators

Genentech, Inc.

Investigators

  • Study Director: Mark D. McKee, MD, AbbVie

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

June 27, 2008

First Submitted That Met QC Criteria

June 27, 2008

First Posted (Estimate)

July 1, 2008

Study Record Updates

Last Update Posted (Estimate)

May 15, 2013

Last Update Submitted That Met QC Criteria

May 7, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M10-300
  • 2007-007081-38 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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