Ignite Creation Date:
2025-12-24 @ 2:44 PM
Ignite Modification Date:
2026-02-25 @ 8:11 PM
Study NCT ID:
NCT00511459
Status:
COMPLETED
Last Update Posted:
2015-10-29
First Post:
2007-08-02
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients
Sponsor:
Amgen
Organization:
Study Overview
Official Title:
A Randomized, 4-Arm, Placebo-Controlled Phase 2 Trial of AMG 386 in Combination With Bevacizumab and Paclitaxel or AMG 386 Plus Paclitaxel as First-Line Therapy in Subjects With Her2-Negative, Metastatic or Locally Recurrent Breast Cancer
Status:
COMPLETED
Status Verified Date:
2015-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.
AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.
AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.
Detailed Description:
Primary Objective: To estimate the treatment effect as measured by progression free survival (PFS) of subjects receiving AMG 386 (at 2 doses) in combination with paclitaxel + bevacizumab relative to paclitaxel + bevacizumab + placebo.
Secondary Objective(s):
* To compare the treatment effect as measured by PFS of subjects receiving open-label 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 (RR, DOR, TTR, TTP) 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
Exploratory Objective(s):
* To explore the pharmacodynamic (PD) response as assessed by changes in blood levels of angiogenic cytokines, tumor apoptosis, and other markers
* To explore the association of histological features and selected immunologic, biochemical, pharmacogenetic, or angiogenic markers in tumor biopsies, plasma, or serum samples with safety and/or efficacy outcomes
Study Design:
This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.
Two hundred twenty subjects will be randomized 1:1:1:1 to each of the following arms:
Arm A: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW Arm B: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW Arm C: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW Arm D: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW To maintain the double-blind in arms A, B, and C, each subject will be infused weekly with a volume of investigational product equivalent to 10 mg/kg AMG 386 IV. Arm D will receive open label AMG 386 and will not receive a placebo for bevacizumab.
Subjects will be discontinued from study treatment at any time for radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death.
Subjects alive at the time of discontinuation of all study medications will be followed for up to 48 months from the date of the last subject enrolled into the trial to evaluate overall survival.
Radiological imaging to assess disease status will be performed every 8 weeks ± 7 days (2 cycles) for 2 years and then every 4 months ± 1 month thereafter during the study until subjects develop radiographic disease progression per the modified RECIST criteria. In addition, any subject who discontinues study drug treatment prior to disease progression will continue to have radiological imaging performed every 8 weeks ± 7 days during the long term follow up period if the subject has not been in the study for 2 years until the subject develops radiographic disease progression or begins a new treatment. If the subject has been on study for 2 years, radiological imaging every 4 months ± 1 month will be performed during long term follow-up period until the subject develops radiographic disease progression or begins a new treatment.
The overall study design is described by a study schema immediately following this synopsis. Amgen Global Safety (AGS) will charter a data review team (DRT) that is independent of the team conducting the study and will review unblinded safety data after 20, 40, and 80 subjects have been randomized and have had the opportunity to receive at least 1 cycle (4 weeks) of study treatment.
Secondary Objective(s):
* To compare the treatment effect as measured by PFS of subjects receiving open-label 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 (RR, DOR, TTR, TTP) 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
Exploratory Objective(s):
* To explore the pharmacodynamic (PD) response as assessed by changes in blood levels of angiogenic cytokines, tumor apoptosis, and other markers
* To explore the association of histological features and selected immunologic, biochemical, pharmacogenetic, or angiogenic markers in tumor biopsies, plasma, or serum samples with safety and/or efficacy outcomes
Study Design:
This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.
Two hundred twenty subjects will be randomized 1:1:1:1 to each of the following arms:
Arm A: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW Arm B: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW Arm C: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW Arm D: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW To maintain the double-blind in arms A, B, and C, each subject will be infused weekly with a volume of investigational product equivalent to 10 mg/kg AMG 386 IV. Arm D will receive open label AMG 386 and will not receive a placebo for bevacizumab.
Subjects will be discontinued from study treatment at any time for radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death.
Subjects alive at the time of discontinuation of all study medications will be followed for up to 48 months from the date of the last subject enrolled into the trial to evaluate overall survival.
Radiological imaging to assess disease status will be performed every 8 weeks ± 7 days (2 cycles) for 2 years and then every 4 months ± 1 month thereafter during the study until subjects develop radiographic disease progression per the modified RECIST criteria. In addition, any subject who discontinues study drug treatment prior to disease progression will continue to have radiological imaging performed every 8 weeks ± 7 days during the long term follow up period if the subject has not been in the study for 2 years until the subject develops radiographic disease progression or begins a new treatment. If the subject has been on study for 2 years, radiological imaging every 4 months ± 1 month will be performed during long term follow-up period until the subject develops radiographic disease progression or begins a new treatment.
The overall study design is described by a study schema immediately following this synopsis. Amgen Global Safety (AGS) will charter a data review team (DRT) that is independent of the team conducting the study and will review unblinded safety data after 20, 40, and 80 subjects have been randomized and have had the opportunity to receive at least 1 cycle (4 weeks) of study treatment.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: