Her2-Negative, Metastatic or Locally Recurrent Breast Cancer MedDRA version: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Interventions
Product Name: AMG 386
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: AMG 386
Current Sponsor code: AMG 386
Concentration unit: mg/ml milligram(s)/millilitre
Concentrat
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Disease Related • Subjects must have histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent. • Measurable or non-measurable disease per modified RECIST guidelines (see Appendix G). • Complete radiology and tumor measurement within 21 days prior to randomization: - Chest: CT / MRI scan with intravenous contrast if the contrast is not medically contraindicated - Abdomen: CT / MRI scan with intravenous contrast if the contrast is not medically contraindicated - Pelvis: CT / MRI scan with intravenous contrast if the contrast is not medically contraindicated - Brain: CT / MRI scan - Bone: Whole body Bone Scintigraphy - Demographic • Female 18 years of age or older at the time the written informed consent is obtained • Subjects of child-bearing potential and sexually active must use an accepted and effective non-hormonal method of contraception (i.e., double barrier method [e.g. condom plus diaphragm]) from signing the informed consent through 6 months - General • Able to tolerate intravenous infusions • ECOG of 0 or 1 (within 14 days prior to randomization) - Laboratory Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to randomization: • Hematological function, as follows: - Absolute neutrophil count (ANC) = 1.5 x 109/L - Platelet count = 100 x 109/L and = 850 x 109/L - Hemoglobin = 9 g/dL - PTT and INR = 1.0 x ULN • Renal function, as follows: - Calculated creatinine clearance > 40 cc/min according to the Cockcroft- Gault formula GFR (mL/min) = (140–age) x actual body weight (kg) (x 0.85 for females) -------------------------------------------- 72 x serum creatinine (mg/dL) - Urinary protein quantitative value of = 30 mg in urinalysis or = 1+ on dipstick, unless quantitative protein is =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Disease Related • Inflammatory Breast Cancer • Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 peripheral neuropathy > grade 1 at randomization • History of arterial or venous thrombosis, including transient ischemic attack (TIA), within 1 year prior to randomization • Adjuvant or neoadjuvant taxane treatment within 12 months of randomization any other adjuvant chemotherapy regimen must be discontinued at least 21 days prior to randomization • Prior chemotherapy, vaccine, or biological therapy 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 disease unless disease progression was subsequently documented prior to 14 days of randomization • Overexpression of HER-2 (gene amplification by FISH or 3+ over expression by immunohistochemistry). - Eligibility of subjects with 2+ immunohistochemistry must be confirmed by a negative FISH assay • Current or prior history of central nervous system metastasis • History of bleeding diathesis or clinically significant bleeding within 6 months prior to randomization • Major surgical procedure within 28 days prior to randomization • Open breast biopsy within 14 days prior to randomization • Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of first dose • Prior malignancy (other than thyroid cancer, in situ cervical cancer, or basal cell cancer of the skin, treated with curative intent and without evidence of disease for = 3 years prior to randomization) • Clinically significant cardiac disease within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication • Non-healing wound, ulcer or fracture • Ongoing or active infection • Known hypersensitivity to paclitaxel or drugs using the vehicle cremophor • Known hypersensitivity to bacterial proteins, or any of the drugs required in this study • Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen • Known active or chronic hepatitis • Uncontrolled hypertension as defined as systolic blood pressure = 150 mm Hg and diastolic blood pressure = 90 mm Hg. Anti-hypertensive medications are allowed if the subject is stable on their current dose at the time of randomization. - Medications • Currently or previously treated with any VEGF or VEGFr inhibitor including, but not limited to, bevacizumab, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AEE-788, BAY 43-9006 (sorafenib) and AMG 706. • Treatment with coumarin-type anticoagulants, (other than low dose prophylaxis for central venous catheters = 1mg/day) within 7 days prior to randomization • Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2 including, but not limited to, AMG 386, XL880, XL820 • Treatment with immune modulators such as cyclosporine or tacrolimus within 30 days prior to randomization • Concomitant therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMS), given for breast cancer prevention or for osteoporosis. Subjects m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To estimate the treatment effect as measured by progression free survival (PFS) of subjects receiving AMG 386 (at two doses) in combination with paclitaxel + bevacizumab relative to paclitaxel + bevacizumab + placebo.;Secondary Objective: • To compare the treatment effect as measured by PFS of subjects receiving openlabel AMG 386 in combination with paclitaxel relative to paclitaxel + bevacizumab + placebo • To compare the treatment effect as measured by PFS of subjects receiving AMG 386 in combination with paclitaxel and bevacizumab relative to paclitaxel + AMG 386 • To evaluate the safety and tolerability of the combination and non-bevacizumab regimens • To estimate other measures (objective response rate, duration of response, overall survival, time to progression, time to response, and percentage change from baseline in the sum of the longest diameters of target lesions) of treatment effect • To evaluate the pharmacokinetics (PK) of AMG 386 and bevacizumab when used in combination • To estimate the incidence of anti-AMG386 antibody formation;Primary end point(s): Progression-free survival (PFS): time from randomization date to date of disease progression per the modified RECIST criteria or death. Subjects not meeting criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date. | — |
Countries
Austria, Belgium, Denmark, Finland, France, Hungary, Netherlands, Spain, United Kingdom
Outcome results
None listed