A Study of AMG 706 or Bevacizumab, in Combination With Paclitaxel Chemotherapy, as Treatment for Breast Cancer

• ClinicalTrials.gov Identifier: NCT00356681
• Recruitment Status: Terminated
• First Posted: July 26, 2006
• Last Update Posted: October 15, 2015
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

To determine if treatment with paclitaxel plus AMG 706 is superior to paclitaxel plus AMG 706 placebo in subjects with HER2 negative locally recurrent or metastatic breast cancer. Also to estimate differences between treatment with paclitaxel plus AMG 706 and paclitaxel plus bevacizumab.

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms; Breast Tumors; Breast Cancer; Locally Recurrent and Metastatic Breast Cancer	Drug: AMG 706 placebo; Drug: Bevacizumab; Drug: AMG 706; Drug: Paclitaxel	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 282 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase 2 Trial of Double-Blind, Placebo Controlled AMG 706 in Combination With Paclitaxel, or Open-Label Bevacizumab in Combination With Paclitaxel, as First Line Therapy in Women With HER2 Negative Locally Recurrent or Metastatic Breast Cancer
• Study Start Date: December 2006
• Actual Primary Completion Date: February 2009
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Arm A Placebo; Blinded AMG 706 placebo plus paclitaxel	Drug: AMG 706 placebo; Blinded placebo; Drug: Paclitaxel; Paclitaxel is an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules.
Experimental: Arm B Experimental; Blinded AMG 706 plus paclitaxel	Drug: AMG 706; AMG 706 is a small organic molecule that has been shown in preclinical pharmacology and PK studies to be a potent, oral, multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively targeting all known VEGF, PDGF and Kit receptors.; Other Name: motesanib diphosphate; Drug: Paclitaxel; Paclitaxel is an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules.
Active Comparator: Arm C Comparator; Open-label bevacizumab plus paclitaxel	Drug: Bevacizumab; Bevacizumab is a recombinant, humanized anti-VEGF monoclonal antibody.; Other Name: Avastin; Drug: Paclitaxel; Paclitaxel is an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules.

Outcome Measures

Primary Outcome Measures :

1. Objective response rate, measured radiologically and assessed by an independent review committee. [ Time Frame: Last patient enrolled + 16 weeks of treatment ]

Secondary Outcome Measures :

1. Progression free survival, duration of response, clinical benefit rate (percentage of subjects with complete response, partial response or stable disease lasting >24 weeks), overall survival and incidence of adverse events. [ Time Frame: >24 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease.
• Measurable disease by RECIST guidelines.
• Tumor (primary or metastatic) must be HER2 negative.
• Adequate organ and hematologic function. Exclusion:
• Taxane treatment within 12 months prior to registration.
• Prior chemotherapy for locally recurrent or metastatic breast cancer (prior endocrine therapy is permitted).
• Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepatic chemoembolization on all sites of measurable disease.
• Current or prior history of central nervous system metastases.
• Peripheral neuropathy ≥ grade 2 (CTCAE v3.0) at registration.
• History of arterial or venous thrombosis within 1 year prior to registration.
• History of bleeding diathesis or bleeding within 14 days of registration.
• Uncontrolled hypertension (systolic >145 mmHg; diastolic >85 mmHg).
• Clinically significant cardiac disease within 12 months of registration.
• Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive.
• Prior treatment with VEGFr targeted therapies.

Contacts and Locations

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Martin M, Roche H, Pinter T, Crown J, Kennedy MJ, Provencher L, Priou F, Eiermann W, Adrover E, Lang I, Ramos M, Latreille J, Jagiello-Gruszfeld A, Pienkowski T, Alba E, Snyder R, Almel S, Rolski J, Munoz M, Moroose R, Hurvitz S, Banos A, Adewoye H, Hei YJ, Lindsay MA, Rupin M, Cabaribere D, Lemmerick Y, Mackey JR; TRIO 010 investigators. Motesanib, or open-label bevacizumab, in combination with paclitaxel, as first-line treatment for HER2-negative locally recurrent or metastatic breast cancer: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Oncol. 2011 Apr;12(4):369-76. doi: 10.1016/S1470-2045(11)70037-7. Epub 2011 Mar 21. Erratum In: Lancet Oncol. 2011 Aug;12(8):722.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT00356681
• Other Study ID Numbers: 20050225; CIRG/TORI 010
• First Posted: July 26, 2006
• Last Update Posted: October 15, 2015
• Last Verified: September 2015

Keywords provided by Amgen:

AMG 706; Paclitaxel; Metastatic Breast Cancer; Antiangiogenic; Bevacizumab

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Niacinamide; Paclitaxel; Bevacizumab; Motesanib diphosphate; Imetelstat; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Vitamin B Complex; Vitamins; Micronutrients