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

Advanced Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00707889
• Other study ID #: M10-300
• Secondary ID: 2007-007081-38
• Status: Completed
• Phase: Phase 2
• First received: June 27, 2008
• Last updated: May 7, 2013
• Start date: October 2008
• Est. completion date: May 2012

Study information

• Verified date: May 2013
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: Ministry of HealthCanada: Health CanadaCzech Republic: State Institute for Drug ControlGreece: National Organization of MedicinesKorea: Food and Drug AdministrationNew Zealand: MedsafePoland: Ministry of HealthPortugal: Health Ethic CommitteeRomania: National Medicines AgencyRussia: Ministry of Health of the Russian FederationSpain: Agencia Española de Medicamentos y Productos SanitariosUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Other known NCT identifiers

• NCT00788411

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Colon
• Adenocarcinoma of the Rectum
• Advanced Colorectal Cancer
• Colorectal Neoplasms
• Rectal Neoplasms

Intervention

Drug:
• ABT-869
12.5 mg QD, tablets taken orally days 1-14 of every 14-day cycle
• bevacizumab
10 mg/kg QD, IV on Day 1 of each 14-day cycle
• oxaliplatin
85 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle
• folinic acid
400 mg/m2 IV, 120 minutes on Day 1 of each 14-day cycle
• fluorouracil
400 mg/m2 IV bolus on Day 1 of each 14-day cycle; followed by 2400 mg/m2 IV infusion 46-48 hours
• ABT-869
7.5 mg QD tablets taken orally days 1-14 of every 14-day cycle

Locations

Country	Name	City	State
Australia	Site Reference ID/Investigator# 18581	Bedford Park
Australia	Site Reference ID/Investigator# 23443	Herston
Belgium	Site Reference ID/Investigator# 18023	Bonheiden
Belgium	Site Reference ID/Investigator# 23646	Brussels
Belgium	Site Reference ID/Investigator# 18026	Leuven
Belgium	Site Reference ID/Investigator# 18022	Roeselare
Brazil	Site Reference ID/Investigator# 26662	Jau
Brazil	Site Reference ID/Investigator# 24245	Porto Alegre
Canada	Site Reference ID/Investigator# 23265	Barrie
Canada	Site Reference ID/Investigator# 21083	Edmonton
Canada	Site Reference ID/Investigator# 22465	Ottawa
Czech Republic	Site Reference ID/Investigator# 22141	Nachod
Greece	Site Reference ID/Investigator# 22289	Heraklion
Greece	Site Reference ID/Investigator# 22286	Thessaloniki
Greece	Site Reference ID/Investigator# 22287	Thessaloniki
Korea, Republic of	Site Reference ID/Investigator# 18281	Seoul
Korea, Republic of	Site Reference ID/Investigator# 18282	Seoul
Korea, Republic of	Site Reference ID/Investigator# 18283	Seoul
New Zealand	Site Reference ID/Investigator# 20281	Wellington South
Poland	Site Reference ID/Investigator# 20141	Olsztyn
Poland	Site Reference ID/Investigator# 17946	Warsaw
Poland	Site Reference ID/Investigator# 38284	Warsaw
Portugal	Site Reference ID/Investigator# 23908	Aveiro
Portugal	Site Reference ID/Investigator# 22324	Coimbra
Portugal	Site Reference ID/Investigator# 23724	Faro
Portugal	Site Reference ID/Investigator# 23964	Lisbon
Romania	Site Reference ID/Investigator# 23303	Baia Mare
Romania	Site Reference ID/Investigator# 23302	Brasov
Romania	Site Reference ID/Investigator# 17962	Bucharest
Romania	Site Reference ID/Investigator# 17964	Bucharest
Romania	Site Reference ID/Investigator# 23304	Bucharest
Romania	Site Reference ID/Investigator# 17961	Cluj Napoca
Romania	Site Reference ID/Investigator# 23305	Craiova
Russian Federation	Site Reference ID/Investigator# 24422	Moscow
Russian Federation	Site Reference ID/Investigator# 24423	Moscow
Russian Federation	Site Reference ID/Investigator# 25063	Moscow
Russian Federation	Site Reference ID/Investigator# 25065	Moscow
Spain	Site Reference ID/Investigator# 22809	A Coruna
Spain	Site Reference ID/Investigator# 22807	Barcelona
Spain	Site Reference ID/Investigator# 22801	Madrid
Spain	Site Reference ID/Investigator# 22804	Madrid
Spain	Site Reference ID/Investigator# 22803	Pamplona Navarra
Spain	Site Reference ID/Investigator# 22800	Santander
United States	Site Reference ID/Investigator# 11341	Chapel Hill	North Carolina
United States	Site Reference ID/Investigator# 8360	Nashville	Tennessee
United States	Site Reference ID/Investigator# 20801	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
AbbVie (prior sponsor, Abbott)	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Czech Republic,  Greece,  Korea, Republic of,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		Radiographic evaluation every 2 months, clinial evaluation every 2 weeks	No
Secondary	Overall survival		from randomization until patient death or alive at 5 years	No
Secondary	12-month overall survival rate		from randomization until patient death or alive at 5 years	No
Secondary	Objective response rate		from randomization until patient death or alive at 5 years	No