Ignite Creation Date:
2024-05-05 @ 6:36 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00511459
Status:
COMPLETED
Last Update Posted:
2015-10-29
First Post:
2007-08-02
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:
Amgen
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 paclitaxelbevacizumab 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 Objectives
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 Objectives
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 andor 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 paclitaxelbevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer
Two hundred twenty subjects will be randomized 1111 to each of the following arms
Arm A Paclitaxel 90 mgm² IV QW 3 on1 off bevacizumab 10 mgkg IV Q2W AMG 386 10 mgkg IV QW Arm B Paclitaxel 90 mgm² IV QW 3 on1 off bevacizumab 10 mgkg IV Q2W AMG 386 3 mgkg IV QW Arm C Paclitaxel 90 mgm² IV QW 3 on1 off bevacizumab 10 mgkg IV Q2W AMG 386 placebo IV QW Arm D Paclitaxel 90 mgm² IV QW 3 on1 off Open Label AMG 386 10 mgkg 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 mgkg 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 Objectives
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 Objectives
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 andor 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 paclitaxelbevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer
Two hundred twenty subjects will be randomized 1111 to each of the following arms
Arm A Paclitaxel 90 mgm² IV QW 3 on1 off bevacizumab 10 mgkg IV Q2W AMG 386 10 mgkg IV QW Arm B Paclitaxel 90 mgm² IV QW 3 on1 off bevacizumab 10 mgkg IV Q2W AMG 386 3 mgkg IV QW Arm C Paclitaxel 90 mgm² IV QW 3 on1 off bevacizumab 10 mgkg IV Q2W AMG 386 placebo IV QW Arm D Paclitaxel 90 mgm² IV QW 3 on1 off Open Label AMG 386 10 mgkg 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 mgkg 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:
None
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?:
None