Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Recurrence

Breast Neoplasms

Breast Diseases

Skin Diseases

Disease Attributes

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Angiogenesis Inhibitors

Imetelstat

Motesanib diphosphate

Tubulin Modulators

Antimitotic Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

AMG 706 50 mg daily + Docetaxel (100 mg/m2 D1 every 21 days)

75 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8 and D15 every 28 days)

AMG 706 50 mg daily + Paclitaxel (90 mg/m2 D1, D8, D15 every 28 days)

75 mg AMG 706 daily + Docetaxel (100 mg/m2, D1 every 21 days)

MTD of AMG 706 + Docetaxel (75mg/m2 D1 every 21 days)

100 mg AMG 706 daily + Docetaxel (100 mg/m2 on D1 every 21 days)

AMG 706 125 mg daily + Docetaxel (100 mg/m2 D1 every 21 days)

AMG 706 125 mg daily + paclitaxel 90 mg/m2 D1, D8, D15 every 28 days

100 mg AMG 706 daily + Paclitaxel (90 mg/m2 on D1, D8, and D15 every 28 days)

Subjects assigned to Arm B, cohorts will receive 75 or 100 mg/m2 of docetaxel (based on cohort assignment) on Day 1 repeated every 21 days (1 cycle). AMG 706 will be administered concurrently on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond.

Subjects assigned to Arm A will receive 90 mg/m2 of paclitaxel on Days 1, 8 and 15 repeated every 28 days (1 cycle). On Arm A, AMG 706 will be concurrently administered on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond.

Subjects assigned to Arm A will receive AMG 706 at 50, 75, 100 or 125 mg daily (based on cohort assignment) on Days 3-28 of Cycle 1, and Days 1-28 of Cycle 2 and beyond in combination wth paclitaxel 90 mg/m2. Paclitaxel will be administered on Days 1, 8 and 15 every 28 days.

Subjects assigned to Arm B will receive AMG 706 at 50, 75, 100 or 125 mg daily(based on cohort assignment) on Days 3-21 of Cycle 1, and Days 1-21 of Cycle 2 and beyond in combination with docetaxel. Docetaxel will be administered at either 75 mg/m2 or 100 mg/m2 on Day 1 every 21 days.

AMG 706

This open-label, dose-finding, multi-center study is designed to determine the safety and the maximum tolerated dose of AMG 706 given once daily in combination with either weekly paclitaxel (Arm A) or once-every-3 week docetaxel (Arm B) in subjects with locally recurrent or metastatic breast cancer. Secondarily, this study will evaluate the pharmacokinetic (PK) profile of AMG 706 in both treatment arms, the PK profile of paclitaxel in Arm A and the PK profile of docetaxel in Arm B. Additionally, this study will assess objective tumor response and duration of response. Exploratory endpoints include the investigation of potential biomarker development and to assess the effects of genetic variation in drug metabolism genes, cancer genes and drug target genes on subject response to AMG 706 in combination with paclitaxel or docetaxel.

Phase1b to Evaluate Safety of AMG706 in Combination With Paclitaxel or Docetaxel for Breast Cancer

An Open-label, Dose-finding Study to Evaluate the Safety of AMG 706 in Combination With Paclitaxel or Docetaxel as Treatment for Locally Recurrent or Metastatic Breast Cancer

Amgen

Micronutrients

Vasodilator Agents

Lipid Regulating Agents

Hematinics

Vitamins

Antibodies

Antibodies, Monoclonal

Bevacizumab

Immunoglobulins

Niacinamide

Niacin

Nicotinic Acids

Antineoplastic Agents, Immunological

Growth Inhibitors

Folic Acid

Vitamin B Complex

Trace Elements

Nicotinamide

Nicotinic Acid

Vitamin B3

Folate

Vitamin B9

AMG 706 placebo

Bevacizumab is a recombinant, humanized anti-VEGF monoclonal antibody.

AMG 706 is a small organic molecule that has been shown in preclinical pharmacology and PK studies to be a potent, oral, multi-kinase inhibitor with anti-angiogenic and anti-tumor activity achieved by selectively targeting all known VEGF, PDGF and Kit receptors.

Paclitaxel is an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules.

To determine if treatment with paclitaxel plus AMG 706 is superior to paclitaxel plus AMG 706 placebo in subjects with HER2 negative locally recurrent or metastatic breast cancer. Also to estimate differences between treatment with paclitaxel plus AMG 706 and paclitaxel plus bevacizumab.

A Study of AMG 706 or Bevacizumab, in Combination With Paclitaxel Chemotherapy, as Treatment for Breast Cancer

A Randomized Phase 2 Trial of Double-Blind, Placebo Controlled AMG 706 in Combination With Paclitaxel, or Open-Label Bevacizumab in Combination With Paclitaxel, as First Line Therapy in Women With HER2 Negative Locally Recurrent or Metastatic Breast Cancer

Trebananib

Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW

Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW

Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW

Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW

AMG 386 Placebo

AMG 386

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.

Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase1b to Evaluate Safety of AMG706 in Combination With Paclitaxel or Docetaxel for Breast Cancer	NCT00322400	Locally Recurre...	Docetaxel Paclitaxel AMG 706	18 Years -	Amgen
A Study of AMG 706 or Bevacizumab, in Combination With Paclitaxel Chemotherapy, as Treatment for Breast Cancer	NCT00356681	Breast Neoplasm... Breast Tumors Breast Cancer Locally Recurre...	AMG 706 placebo Bevacizumab AMG 706 Paclitaxel	18 Years -	Amgen
A Study of AMG 706 or Bevacizumab, in Combination With Paclitaxel Chemotherapy, as Treatment for Breast Cancer	NCT00356681	Breast Neoplasm... Breast Tumors Breast Cancer Locally Recurre...	AMG 706 placebo Bevacizumab AMG 706 Paclitaxel	18 Years -	Amgen
Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients	NCT00511459	Locally Recurre...	AMG 386 Placebo AMG 386 Bevacizumab AMG 386 AMG 386 Paclitaxel	18 Years -	Amgen

Spots Global Cancer Trial Database for locally recurrent and metastatic breast cancer