To determine the clinical efficacy and toxicity of ABT-869 in combination with paclitaxel in the first-line treatment of subjects with metastatic breast cancer.
ID
Source
Brief title
Condition
- Breast neoplasms malignant and unspecified (incl nipple)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy analysis will be a comparison of PFS (radiographic
progression, clinical progression, or death) distributions between the
Paclitaxel + ABT-869 and Paclitaxel + placebo treatment groups.
PFS will be defined as the number of days from the day the subject is
randomized to the day the subject experiences an event of disease progression
or to the date of death if dieases progression is not reached.
Secondary outcome
Secundary efficacy analysis comparing the effects of Paclitaxel + ABT-869
versus Paclitaxel + placebo on the following set of endpoints will also be
performed: overall survival, 12-month survival rate, time of disease
progression (TTP). objective response rate, maximum percent reduction in tumor
size and duration of respons.
In addition to the primary and secundary efficacy analysis, tertiary efficacy
analyses comparing the effect of
Paclitaxel + ABT-869 versus Paclitaxel + placebo on Quality of Life (Fact-B)
and performance status will be performed
Background summary
ABT-869 is an experimental drug that affects cancer cells by blocking the
growth of blood vessels and by killing cancer cells. Laboratory and animal
studies have shown that the ABT-869 is active against many cancer cell types.
ABT-869 has been tested in adult subjects with cancers resistant to standard
treatments but has not yet been proven to result in antitumor effects in these
subjects.
Study objective
To determine the clinical efficacy and toxicity of ABT-869 in combination with
paclitaxel in the first-line treatment of subjects with metastatic breast
cancer.
Study design
This is a phase 2, randomised, placebo-controlled, double blind, multicenter
study of the efficacy and tolerability of the ABT-869 in combination with
paclitaxel versus paclitaxel alone in subjects with documented metastatic
breast cancer in the first line metastatic therapy setting.
Intervention
All patients receive standard Paclitaxel (90 mg/m2) on day 1, 8 and 15 of each
28-day cycle via IV infusion. Dosing of oral ABT-869/placebo (0.20 mg/kg QD)
will occur with the start of the paclitaxel infusion on cycle day 1.
Study burden and risks
Screening must be performed within 21 days of study day 1. Vital signs,
hematology labs and performance status assessment will be performed on day 1.
Baseline radiographic tumor assessments (CT scan) will be conducted within 21
days prir to the first dose of study drug. Radiographic tumor assessments will
be conducted after every 3 cyclus (12 weeks) of the study drug.
A baseline bone scan will be conducted within 21 days prior to the first dose
of study drug and will be repeated as clinically indicated. Also ECG and MUGA /
echocardiogram will be performed within 21 days prior first dose and the MUGA /
echocardiogram will be performed at the end of every 2 cycus for the first 4
cyclus, then at the end of every 4 cyclus thereafter.
Study visits will be conducted at day 1, 8 and 15. When an investigator has
determined that a subject should discontinue the study, a final visit will be
conducted.
All subjects will have one follow-up visit approximately 30 days after the last
dose of ABT-869/placebo. If the subject discontinues the study due to
toxicities attributable to ABT-869, additional follow-up visits will be
conducted at least every 30 days untill the toxicity diminishes to an
acceptable level or until the toxicity is determined to be stable or
irreversible.
Subjects will have survival assessments following discontinuation of study at
interval of every three months for 2 years, an interval of 6 months for the
following 3 years until the subject has died or has become lost-to follow-up.
200 Abbott Park Rd.
IL 60064-6146
Verenigde Staten
200 Abbott Park Rd.
IL 60064-6146
Verenigde Staten
Listed location countries
Age
Inclusion criteria
- 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
Exclusion criteria
- 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.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-005949-38-NL |
| ClinicalTrials.gov | NCT00645177 |
| CCMO | NL24730.098.08 |