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

NCT00707889 | Completed Phase 2

• 2 other identifiers: M10-3002007-007081-38
• Study Type: interventional
• Target: 159
• Locations: 14 countries
• Sites: 46

Brief Summary

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

Conditions

Advanced Colorectal Cancer; Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Radiographic evaluation every 2 months, clinial evaluation every 2 weeks

Secondary Outcomes (3)

• Overall survival

  from randomization until patient death or alive at 5 years

• 12-month overall survival rate

  from randomization until patient death or alive at 5 years

• Objective response rate

  from randomization until patient death or alive at 5 years

Study Arms (3)

A

ACTIVE COMPARATOR

Open-label to Bevacizumab plus mFOLFOX6

Drug: bevacizumab; Drug: oxaliplatin; Drug: folinic acid; Drug: fluorouracil

B

ACTIVE COMPARATOR

Open-label to High-dose ABT-869 arm plus mFOLFOX6

Drug: ABT-869; Drug: oxaliplatin; Drug: folinic acid; Drug: fluorouracil

C

ACTIVE COMPARATOR

Open-label to low-dose ABT-869 arm plus mFOLFOX6

Drug: oxaliplatin; Drug: folinic acid; Drug: fluorouracil; Drug: ABT-869

Interventions

ABT-869 DRUG

12.5 mg QD, tablets taken orally days 1-14 of every 14-day cycle

B

bevacizumab DRUG

10 mg/kg QD, IV on Day 1 of each 14-day cycle

A

oxaliplatin DRUG

85 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle

Also known as: mFOLFOX6 regimen

A; B; C

folinic acid DRUG

400 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle

Also known as: mFOLFOX6 regimen

A; B; C

fluorouracil DRUG

400 mg/m2 IV bolus on Day 1 of each 14-day cycle; followed by 2400 mg/m2 IV infusion 46-48 hours

Also known as: mFOLFOX6 regimen

A; B; C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead
• Genentech, Inc.: collaborator

Study Sites (46)

Site Reference ID/Investigator# 11341

Chapel Hill, North Carolina, 27599-7305, United States

Location

Site Reference ID/Investigator# 20801

Philadelphia, Pennsylvania, 19107, United States

Location

Site Reference ID/Investigator# 8360

Nashville, Tennessee, 37232-6307, United States

Location

Site Reference ID/Investigator# 18581

Bedford Park, 5042, Australia

Location

Site Reference ID/Investigator# 23443

Herston, 4029, Australia

Location

Site Reference ID/Investigator# 18023

Bonheiden, 2820, Belgium

Location

Site Reference ID/Investigator# 23646

Brussels, 1200, Belgium

Location

Site Reference ID/Investigator# 18026

Leuven, 3000, Belgium

Location

Site Reference ID/Investigator# 18022

Roeselare, 8800, Belgium

Location

Site Reference ID/Investigator# 26662

Jaú, 17210-120, Brazil

Location

Site Reference ID/Investigator# 24245

Porto Alegre, 90610-000, Brazil

Location

Site Reference ID/Investigator# 23265

Barrie, L4M 6M2, Canada

Location

Site Reference ID/Investigator# 21083

Edmonton, T6G 1Z2, Canada

Location

Site Reference ID/Investigator# 22465

Ottawa, K1H 8L6, Canada

Location

Site Reference ID/Investigator# 22141

Náchod, 54769, Czechia

Location

Site Reference ID/Investigator# 22289

Heraklion, 71110, Greece

Location

Site Reference ID/Investigator# 22286

Thessaloniki, 54007, Greece

Location

Site Reference ID/Investigator# 22287

Thessaloniki, 56403, Greece

Location

Site Reference ID/Investigator# 20281

Wellington South, 6021, New Zealand

Location

Site Reference ID/Investigator# 20141

Olsztyn, 10513, Poland

Location

Site Reference ID/Investigator# 17946

Warsaw, 02-781, Poland

Location

Site Reference ID/Investigator# 38284

Warsaw, 04-125, Poland

Location

Site Reference ID/Investigator# 23908

Aveiro, 3814-501, Portugal

Location

Site Reference ID/Investigator# 22324

Coimbra, 3001-651, Portugal

Location

Site Reference ID/Investigator# 23724

Faro, 8000-386, Portugal

Location

Site Reference ID/Investigator# 23964

Lisbon, 1099-023, Portugal

Location

Site Reference ID/Investigator# 23303

Baia Mare, 430031, Romania

Location

Site Reference ID/Investigator# 23302

Brasov, 500117, Romania

Location

Site Reference ID/Investigator# 17962

Bucharest, 022328, Romania

Location

Site Reference ID/Investigator# 17964

Bucharest, 022328, Romania

Location

Site Reference ID/Investigator# 23304

Bucharest, 050098, Romania

Location

Site Reference ID/Investigator# 17961

Cluj-Napoca, 400015, Romania

Location

Site Reference ID/Investigator# 23305

Craiova, 200385, Romania

Location

Site Reference ID/Investigator# 24422

Moscow, 115478, Russia

Location

Site Reference ID/Investigator# 25063

Moscow, 115478, Russia

Location

Site Reference ID/Investigator# 25065

Moscow, 117997, Russia

Location

Site Reference ID/Investigator# 24423

Moscow, 143423, Russia

Location

Site Reference ID/Investigator# 18281

Seoul, 110-744, South Korea

Location

Site Reference ID/Investigator# 18283

Seoul, 135-710, South Korea

Location

Site Reference ID/Investigator# 18282

Seoul, 138-736, South Korea

Location

Site Reference ID/Investigator# 22809

A Coruña, 15006, Spain

Location

Site Reference ID/Investigator# 22807

Barcelona, 08907, Spain

Location

Site Reference ID/Investigator# 22804

Madrid, 28034, Spain

Location

Site Reference ID/Investigator# 22801

Madrid, 28050, Spain

Location

Site Reference ID/Investigator# 22803

Pamplona Navarra, 31008, Spain

Location

Site Reference ID/Investigator# 22800

Santander, 39008, Spain

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

linifanib; Bevacizumab; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mark D. McKee, MD

  AbbVie

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2008
• First Posted: July 1, 2008
• Study Start: October 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: May 15, 2013

Record last verified: 2013-05

Locations

NZ (1); RU (4); KR (3); PT (4); BR (2); BE (4); AU (2); US (3); RO (7); PL (3); CA (3); ES (6); CZ (1); GR (3)