A Phase 2 Randomized, Placebo-Controlled, Double-Blind Study of ABT-869 in Combination With Paclitaxel Versus Paclitaxel Alone as First-line Treatment in Subjects With Locally Recurrent or Metastatic Breast Cancer
- Conditions
- breast cancerfirst-line treatment10006291
- Registration Number
- NL-OMON32901
- Lead Sponsor
- Abbott
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 8
- The subject is female and * 18 years of age.
- The subject is diagnosed with adenocarcinoma of the breast.
- The subject must have metastatic disease or locally recurrent disease that is not amenable to local treatment (surgical or radiation) with curative intent.
- The subject must have received no prior chemotherapy for locally recurrent or metastatic breast cancer.
- At least 12 months have passed since the subject received prior adjuvant or neoadjuvant cytotoxic chemotherapy (including prior taxane therapy and prior anti-angiogenic therapy [i.e., bevacizumab or a TKI]).
- The subject does not have HER-2 *overexpression (3+) breast cancer (unless treated previously with trastuzumab [Herceptin] or lapatinib).
- The subject has measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT scan as defined by RECIST (for subjects in the randomized portion only).
- The subject has an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
- The subject must have adequate bone marrow, renal and hepatic function
- The subject has received anti-cancer therapy (other than chemotherapy) including investigational agents (any agent not approved for use in humans), immunotherapy, anti-cancer Chinese medicine/herbal remedies, or biologic therapy within 21 days or within a period defined by 5 half lives if the previous agent was a chronically dosed, targeted therapy (e.g., trastuzumab), whichever is shorter, prior to Study Day 1. Clinically significant adverse effects/toxicities of the previous therapy must have recovered to * Grade 1.
- The subject has had major surgery within 21 days of Study Day 1.
- The subject has received radiation therapy (including palliative radiation) within 14 days of Study Day 1.
- The subject has received anti-cancer hormonal therapy (e.g., tamoxifen) within 14 days of Study Day 1.
- The subject has symptomatic or untreated brain or meningeal metastases.
- The subject has hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Crempahor) not able to be controlled with medication.
- The subject has proteinuria CTC grade > 1 at baseline as measured by a UPC ratio of > 1 and confirmed by a 24-hour urine collection.
- The subject is receiving therapeutic anticoagulation therapy. Low dose anticoagulation (e.g., low dose warfarin) for catheter prophylaxis will be permitted.
- The subject has a history of, or currently exhibits, clinically significant cancer related events of bleeding (e.g., gross hemoptysis defined as bright red blood of at least * teaspoon or 2.5 mL per episode within 3 months prior to randomization unless definitively treated with surgery or radiation) or the subject has a recent history of (within 4 weeks of Study Day 1) or currently exhibits other clinically significant signs of bleeding.
- The subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure (BP) > 100 mmHg; or systolic blood pressure (BP) > 150 mmHg. Subjects may be re-screened if blood pressure is shown to be controlled with or without intervention.
- The subject has a history of myocardial infarction, stroke, or transient ischemic attack (TIA) within 6 months of Study Day 1.
- The subject has a documented left ventricular (LV) ejection fraction < 50%.
- The subject has known autoimmune disease with renal involvement (e.g., lupus).
- The subject is receiving combination anti-retroviral therapy for HIV.
- The subject is pregnant or breast-feeding.
- The subject has clinically significant uncontrolled condition(s) including but not limited to:
active uncontrolled infection,
symptomatic congestive heart failure,
unstable angina pectoris or cardiac arrhythmia,
history of adrenal insufficiency,
psychiatric illness/social situation that would limit compliance with study
requirements.
- The subject has active ulcerative colitis, Crohn's disease, celiac disease or any other conditions that interfere with absorption.
- The subject has had another active malignancy within the past 5 years except for cervical cancer in situ, in situ carcinoma of the bladder or non-melanoma carcinoma of the skin. Questions regarding inclusion of individual subjects should be directed to the Abbott Medical Monitor.
- The subject has a medical condition, which in the opinion of the study investigator, places them at an unacceptably high risk for toxicities.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary efficacy analysis will be a comparison of PFS (radiographic<br /><br>progression, clinical progression, or death) distributions between the<br /><br>Paclitaxel + ABT-869 and Paclitaxel + placebo treatment groups.<br /><br>PFS will be defined as the number of days from the day the subject is<br /><br>randomized to the day the subject experiences an event of disease progression<br /><br>or to the date of death if dieases progression is not reached. </p><br>
- Secondary Outcome Measures
Name Time Method <p>Secundary efficacy analysis comparing the effects of Paclitaxel + ABT-869<br /><br>versus Paclitaxel + placebo on the following set of endpoints will also be<br /><br>performed: overall survival, 12-month survival rate, time of disease<br /><br>progression (TTP). objective response rate, maximum percent reduction in tumor<br /><br>size and duration of respons.<br /><br><br /><br>In addition to the primary and secundary efficacy analysis, tertiary efficacy<br /><br>analyses comparing the effect of<br /><br>Paclitaxel + ABT-869 versus Paclitaxel + placebo on Quality of Life (Fact-B)<br /><br>and performance status will be performed</p><br>