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

Sponsor

Amgen (Industry)

Overall Status

Terminated

CT.gov ID

NCT00356681

Collaborator

(none)

282

Enrollment

Arms

Duration (Months)

Study Details

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

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 :

Dec 1, 2006

Actual Primary Completion Date :

Feb 1, 2009

Actual Study Completion Date :

Aug 1, 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 Names: 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 Names: Avastin Drug: Paclitaxel Paclitaxel is an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules.

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 Names:

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 Names:

Avastin

Drug: Paclitaxel

Paclitaxel is an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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. [>24 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.