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: Metastatic breast cancer; MedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer

• Registration Number: EUCTR2007-005949-38-CZ
• Lead Sponsor: Abbott GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-06-18
• Last Update Posted: 5 August 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 90

Inclusion Criteria

1. The subject is female and = 18 years of age.
2. The subject is diagnosed with adenocarcinoma of the breast.
3. The subject must have metastatic disease or locally recurrent disease that is not
amenable to local treatment (surgical or radiation) with curative intent.
4. The subject must have received no prior chemotherapy for locally recurrent or
metastatic breast cancer.
5. 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]).
6. The subject does not have HER-2 –overexpression (3+) breast cancer (unless
treated previously with trastuzumab [Herceptin] or lapatinib).
7. 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).
8. The subject has an Eastern Cooperative Oncology Group (ECOG) performance
score of 0-1.
9. The subject must have adequate bone marrow, renal and hepatic function as
follows:
a. Bone Marrow: absolute neutrophil count (ANC) = 1,500/mm3 (1.5 × 109/L); platelets = 100,000/mm3 (100 × 109/L); hemoglobin = 9.0 g/dL (1.4 mmol/L);
b. Renal function: serum creatinine = 2.0 mg/dL (0.81 mmol/L);
c. Hepatic function: AST and ALT = 1.5 × ULN unless liver metastases are
present, then AST and ALT = 5.0 × ULN; bilirubin = 1.5 mg/dL (0.026 mmol/L).
10. The subject must have PTT = 1.5 × ULN and INR = 1.5.
11. Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to initiation of treatment and/or post menopausal women must be
amenorrheic for at least 12 months to be considered of non-childbearing potential.
Women of childbearing potential must agree to use adequate contraception (one of
the following listed below) prior to study entry, for the duration of study
participation and up to two months following completion of therapy.
? Total abstinence from sexual intercourse (minimum one complete menstrual
cycle);
? A vasectomized partner;
? Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal
ring with spermicidal jellies or cream).
12. The subject is capable of understanding and complying with parameters as
outlined in the protocol and able to sign and date the informed consent, approved
by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB),
prior to the initiation of any screening or study-specific procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. 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.
2. The subject has had major surgery within 21 days of Study Day 1.
3. The subject has received radiation therapy (including palliative radiation) within
14 days of Study Day 1.
4. The subject has received anti-cancer hormonal therapy (e.g., tamoxifen) within
14 days of Study Day 1.
5. The subject has symptomatic or untreated brain or meningeal metastases. CT
scans are not required to rule out brain or meningeal metastases unless there is a
clinical suspicion of central nervous system disease. Subjects with treated brain
metastases that are radiographically or clinically stable for at least 4 weeks after
therapy and have no evidence of cavitation or hemorrhage in the brain lesion are eligible providing that they are asymptomatic and do not require corticosteroids
(must have discontinued steroids at least 1 week prior to Study Day 1).
6. The subject has hypersensitivity to paclitaxel or to other drugs formulated with
polyethoxylated castor oil (Crempahor) not able to be controlled with medication.
7. 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.
8. The subject is receiving therapeutic anticoagulation therapy. Low dose
anticoagulation (e.g., low dose warfarin) for catheter prophylaxis will be permitted.
9. 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 ½ 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.
10. 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.
11. The subject has a history of myocardial infarction, stroke, or transient ischemic
attack (TIA) within 6 months of Study Day 1.
12. The subject has a documented left ventricular (LV) ejection fraction < 50%.
13. The subject has known autoimmune disease with renal involvement (e.g., lupus).
14. The subject is receiving combination anti-retroviral therapy for HIV.
15. The subject is pregnant or breast-feeding.
16. 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.
17. The subject has active ulcerative colitis, Crohn's disease, celiac disease or any
other conditions that interfere with absorption.
18. The subject has had another

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: To evaluate overall survival and other efficacy endpoints, as well as the safety and tolerability of the combination. The tertiary objectives are to evaluate quality of life and performance status.;Main Objective: To assess if the addition of oral ABT-869 to paclitaxel can prolong progression-free survival (PFS) compared to paclitaxel alone in the first line treatment of subjects with metastatic breast cancer.;Primary end point(s): The primary endpoint of the study is progression free survival. The secondary endpoints of the study will be overall survival, 12-month survival rate, time to disease progression, objective response rate, best response rate, maximum percent reduction in tumor size, duration of response as well as the safety and tolerability of the combination. The tertiary endpoints are quality of life and performance status.