None listed
Conditions
Brief summary
The purpose of this study is to test a new anticancer drug, AMG 706, which targets the blood vessels of the tumour. Evidence suggests that the formation of new blood vessels within the tumour is critical in the progression of solid tumours, including breast cancer. Of the numerous factors that affect the growth of these blood vessels, vascular endothelial growth factor (VEGF) is likely one of the most, if not the most, important molecules regulating new blood vessel formation and subsequent invasion and metastasis. As a result, agents that inhibit VEGF (such as those drugs being used in this trial) may prevent this tumour vascular invasion and thereby block the growth of the tumour.
Interventions
Eligible patients will be randomised in a 3-arm design to receive one of the following:
Arm B : Paclitaxel 90mg/m2 IV over 1 hour every week for 3 weeks (days 1, 8, 15, of each 28 day cycle) and blinded AMG 706 125mg orally every day.
Arm C : Paclitaxel 90mg/m2 IV over 1 hour every week for 3 weeks (days 1, 8, 15, of each 28 day cycle) and open label bevacizumab 10mg/kg IV following paclitaxel treatment on week 1 and week 3 of each cycle.
Treatment will be continued until disease progression,
Eligible patients will be randomised in a 3-arm design to receive one of the following: Arm B : Paclitaxel 90mg/m2 IV over 1 hour every week for 3 weeks (days 1, 8, 15, of each 28 day cycle) and blinded AMG 706 125mg orally every day. Arm C : Paclitaxel 90mg/m2 IV over 1 hour every week for 3 weeks (days 1, 8, 15, of each 28 day cycle) and open label bevacizumab 10mg/kg IV following paclitaxel treatment on week 1 and week 3 of each cycle. Treatment will be continued until disease progression, unacceptable toxicity or withdrawal of patient consent.
Sponsors
Amgen Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Confirmed HER2 negative locally recurrent or metastatic breast cancer (locally recurrent disease must not be amenable to resection with curative intent); measurable disease per RECIST (Response Evaluation Criteria in Solid Tumor) guidelines; complete radiology and tumor measurement within 4 weeks (28 days) prior to randomization; ECOG Performance Status of 0 or 1; adequate organ and hematological function; negative pregnancy test within 7 days prior registration for patients of child-bearing potential and sexually active; written informed consent signed prior to any study-related procedures.
Exclusion criteria
1. Adjuvant or neoadjuvant taxane treatment within 12 months of randomization. Any other adjuvant chemotherapy regimen must be discontinued at least 3 weeks (21 days) prior to study randomisation.2. Prior chemotherapy for locally recurrent or metastatic breast cancer (prior endocrine therapyis permitted).3. Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepaticchemoembolization on all sites of measurable disease unless disease progression was subsequently documented on at least one of these sites.4. Current or prior history of central nervous system metastasis.5. Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 peripheral neuropathy > grade 2 at registration.6. Average systolic blood pressure > 145 mm Hg or average diastolic blood pressure > 85 mm Hg (average blood pressure of the 3 separate blood pressure values measured according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure).7. History of arterial or venous thrombosis within 1 year prior to randomisation.8. History of bleeding diathesis or bleeding within 14 days of randomisation.9. Major surgical procedure within 4 weeks (28 days) prior to randomisation.10. Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of randomisation.11. Known positive test for human immunodeficiency virus (HIV), hepatitis C, or malignancy (other than in situ cervical cancer, or basal cell cancer of the skin), unless treated with curative intent and without evidence of disease for = 3 years before study randomisation.12. Clinically significant cardiac disease within 12 months of study randomisation, including myocardial infarction, unstable angina, grade II or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or ongoing arrhythmias requiring medication or pacemaker.13. Non-healing wound, ulcer or fracture.14. Ongoing or active infection.15. Positive hepatitis B surface antigen.16. Known chronic hepatitis.
Outcome results
None listed