Locally Recurrent and Metastatic Breast Cancer Clinical Trial
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
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.
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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00807859 -
Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer
|
Phase 1 | |
| Completed |
NCT00322400 -
Phase1b to Evaluate Safety of AMG706 in Combination With Paclitaxel or Docetaxel for Breast Cancer
|
Phase 1 | |
| Terminated |
NCT00356681 -
A Study of AMG 706 or Bevacizumab, in Combination With Paclitaxel Chemotherapy, as Treatment for Breast Cancer
|
Phase 2 |