HER2 Negative Locally Recurrent or Metastatic Breast Cancer MedDRA version: 14.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AMG 706
Product Code: AMG 706
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Motesanib diphosphate
Current Sponsor code: AMG 706
Other descriptive name: Motesanib
Concentra
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent must be obtained prior to any study-related procedures. 2. 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. 3. Measurable disease per RECIST ( Response Evaluation Criteria in Solid Tumor) guidelines. 4. Complete radiology and tumor measurement within 4 weeks (28 days) prior to registration: a. Chest: CT scan with intravenous contrast if the contrast is not medically contraindicated. b. Abdomen: CT scan with intravenous and oral contrast if the contrast is not medically contraindicated. c. Pelvis: CT scan with intravenous and oral contrast if the contrast is not medically contraindicated. d. Brain: CT scan or MRI e. Bone: Whole body Bone Scintigraphy. 5. Tumor (primary or metastatic) must be HER2 negative by fluorescence in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) or 0, 1+ overexpression by immuno- histochemistry. 6. Female 18 years of age or older at the time the written informed consent is obtained. 7. ECOG Performance Status of 0 or l. 8. Adequate organ and hematological function as evidenced by the following laboratory studies within 2 weeks (14 days) of study registration, unless stated otherwise: a. Cardiac function b. Hematological function c. Renal function d. Hepatic function 9. Subjects of child- bearing potential and sexually active must provide a negative pregnancy test within 7 days prior to registration and use an accepted and effective non- hormonal method of contraception during study treatment and up to 6 months after last dose of study Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 236 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 46
Exclusion criteria
Exclusion criteria: Disease Related 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 registration. 2. Prior chemotherapy for locally recurrent or metastatic breast cancer ( prior endocrine therapy is permitted). 3. Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepatic chemoembolization on all sites of measurable disease unless progression was subsequently documented on at least one of these sites. Medications 4. Currently or previously treated with bevacizumab or small molecule inhibitors of VEGF including, but not limited to, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AZD 6474, AEE- 788, BAY 43- 9006 (sorafenib) and AMG 706. 5. Treatment with coumadin anticoagulants, (other than low dose prophylaxis for central venous catheters < 1mg/ d) within 7 days prior to study registration. 6. Treatment with rifampin, carbamazepine, rifabutin or phenobarbital within 14 days prior to study registration. General 7. Any condition which in the investigator’s opinion makes the subject unsuitable for study participation 8. Participation in other investigational device drug trials, or administration of other investigational treatments within 30 days prior to study registration. 9. Pregnant ( i. e., positive beta- human chorionic gonadotropin test) or breast feeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The primary analysis for the objective response rate will be performed when all subjects who are receiving protocol specified therapy have at least their second radiological image (i.e., the radiological imaging at week 16). An updated analysis will be performed when every subject on the study receiving protocol specified therapy have at least 10 months after first dose of study treatment. ;Main Objective: The primary objective of the study is to determine if treatment with paclitaxel and AMG 706 is superior to paclitaxel plus AMG 706 placebo in subjects with HER2 negative locally recurrent or metastatic breast cancer, based on objective response rates.;Secondary Objective: • To estimate the differences in progression- free survival time, clinical benefit, overall survival and duration of response between Arm A (paclitaxel plus AMG 706 placebo) and Arm B (paclitaxel plus AMG 706). • To estimate the differences in objective response rate, progression- free survival time, clinical benefit, overall survival and duration of response between Arm B (paclitaxel plus AMG 706) and Arm C (paclitaxel plus bevacizumab) • To evaluate safety and tolerability in the three treatment arms;Primary end point(s): Primary Endpoint as defined by RECIST Objective Response Rate: the percentage of subjects assigned to a treatment arm with a confirmed best independent review committee. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • To estimate the differences in progression-free survival time, clinical benefit, overall survival and duration of response between Arm A (paclitaxel plus placebo) and Arm B (paclitaxel plus motesanib). • To estimate the differences in objective response rate, progression-free survival time, clinical benefit, overall survival and duration of response between Arm B (paclitaxel plus motesanib) and Arm C (paclitaxel plus bevacizumab). • To evaluate safety and tolerability in the 3 treatment arms. ;Timepoint(s) of evaluation of this end point: The primary analysis for the objective response rate will be performed when all subjects who are receiving protocol specified therapy have at least their second radiological image (i.e., the radiological imaging at week 16). An updated analysis will be performed when every subject on the study receiving protocol specified therapy have at least 10 months after first dose of study treatment. | — |
Countries
Australia, Canada, Germany, Hong Kong, Hungary, India, Ireland, New Zealand, Spain, United States
Contacts
Public ContactIHQ Medical Info – Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed