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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00511459




Registration number
NCT00511459
Ethics application status
Date submitted
2/08/2007
Date registered
3/08/2007
Date last updated
29/10/2015

Titles & IDs
Public title
Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients
Scientific 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
Secondary ID [1] 0 0
20060341
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Recurrent and Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AMG 386 Placebo
Treatment: Drugs - AMG 386
Treatment: Drugs - Bevacizumab
Treatment: Drugs - AMG 386
Treatment: Drugs - AMG 386
Treatment: Drugs - Paclitaxel

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

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

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

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


Treatment: Drugs: AMG 386 Placebo
AMG 386 Placebo [blinded]

Treatment: Drugs: AMG 386
AMG 386 3mg/kg IV QW [blinded]

Treatment: Drugs: Bevacizumab
Bevacizumab 10mg/kg IV Q2W

Treatment: Drugs: AMG 386
AMG 386 10mg/kg IV QW [Open-Label]

Treatment: Drugs: AMG 386
AMG 386 10mg/kg IV QW [blinded]

Treatment: Drugs: Paclitaxel
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS)
Timepoint [1] 0 0
3 YEARS
Secondary outcome [1] 0 0
Objective Response (OR)
Timepoint [1] 0 0
3 YEARS
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
3 YEARS
Secondary outcome [3] 0 0
Time to response
Timepoint [3] 0 0
3 YEARS
Secondary outcome [4] 0 0
Overall Survival
Timepoint [4] 0 0
3 YEARS
Secondary outcome [5] 0 0
Time to progression (TTP)
Timepoint [5] 0 0
3 YEARS
Secondary outcome [6] 0 0
Incidence of AEs and significant laboratory changes
Timepoint [6] 0 0
3 YEARS
Secondary outcome [7] 0 0
AMG 386 Pharmakokinetic parameters
Timepoint [7] 0 0
3 YEARS
Secondary outcome [8] 0 0
Incidence of the occurrence of anti-AMG 386 antibody formation
Timepoint [8] 0 0
3 YEARS

Eligibility
Key inclusion criteria
- Subjects must have 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.

- Measurable or non-measurable disease per modified RECIST guidelines

- ECOG of 0 or 1 (within 14 days prior to randomization)

- Adequate organ and hematological function as evidenced by the following laboratory
studies within 14 days prior to randomization:

• Cardiac function, as follows:

- Normal sinus rhythm (no significant ECG changes)

- Left ventricular ejection fraction = LLN, as determined by echocardiogram or MUGA
scan, according to institutional standards within 28 days prior to randomization
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Inflammatory Breast Cancer

- Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 peripheral
neuropathy > grade 1 at randomization

- History of arterial or venous thrombosis, including transient ischemic attack (TIA),
within 1 year prior to randomization

- Adjuvant or neoadjuvant taxane treatment within 12 months of randomization. Any other
adjuvant chemotherapy regimen must be discontinued at least 21 days prior to
randomization

- Prior chemotherapy, vaccine, or biological therapy for locally recurrent or metastatic
breast cancer (prior endocrine therapy is permitted)

- Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepatic
chemoembolization on all sites of disease unless disease progression was subsequently
documented 14 days prior to randomization.

- Overexpression of HER-2 (gene amplification by FISH or 3+ over expression by
immunohistochemistry).

- Current or prior history of central nervous system metastasis

- History of bleeding diathesis or clinically significant bleeding within 6 months prior
to randomization

- Major surgical procedure within 28 days prior to randomization

- Open breast biopsy within 14 days prior to randomization

- Minor surgical procedure, placement of access device, or fine needle aspiration within
7 days of first dose

- Prior malignancy (other than thyroid cancer, in situ cervical cancer, or basal cell
cancer of the skin, treated with curative intent and without evidence of disease for =
3 years prior to randomization)

- Clinically significant cardiac disease within 12 months prior to randomization,
including myocardial infarction, unstable angina, grade 2 or greater peripheral
vascular disease, cerebrovascular accident, transient ischemic attack, congestive
heart failure, or arrhythmias not controlled by outpatient medication

- Non-healing wound, ulcer or fracture

- Known hypersensitivity to paclitaxel or drugs using the vehicle cremophor

- Known hypersensitivity to bacterial proteins, or any of the drugs required in this
study

- Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis
B surface antigen

- Known active or chronic hepatitis

- Uncontrolled hypertension as defined as systolic blood pressure = 150 mm Hg and
diastolic blood pressure = 90 mm Hg. Anti-hypertensive medications are allowed if the
subject is stable on their current dose at the time of randomization

- Currently or previously treated with any VEGF or VEGFr inhibitor, including but not
limited to, bevacizumab, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AEE-788,
BAY 43-9006 (sorafenib) and AMG 706.

- Treatment with coumarin-type anticoagulants, (other than low dose prophylaxis for
central venous catheters = 1mg/day) within 7 days prior to randomization

- Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1
or TIE-2 including, but not limited to, AMG 386, XL880, XL820

- Treatment with immune modulators such as cyclosporine and tacrolimus within 30 days
prior to randomization

- Concomitant therapy with any hormonal agent such as raloxifene, tamoxifen, or other
selective estrogen receptor modulators (SERMS), given for breast cancer prevention or
for osteoporosis. Subjects must have discontinued these agents 28 days prior to
randomization

- Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2014
Sample size
Target
Accrual to date
Final
228
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Research Site - Kurralta Park
Recruitment hospital [2] 0 0
Research Site - Epping
Recruitment hospital [3] 0 0
Research Site - Fitzroy
Recruitment hospital [4] 0 0
Research Site - Footscray
Recruitment hospital [5] 0 0
Research Site - Malvern
Recruitment hospital [6] 0 0
Research Site - Perth
Recruitment postcode(s) [1] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [2] 0 0
3076 - Epping
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3011 - Footscray
Recruitment postcode(s) [5] 0 0
3144 - Malvern
Recruitment postcode(s) [6] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
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United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
New Hampshire
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
South Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
Austria
State/province [15] 0 0
Innsbruck
Country [16] 0 0
Austria
State/province [16] 0 0
Wels
Country [17] 0 0
Austria
State/province [17] 0 0
Wien
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Belgium
State/province [19] 0 0
Liege
Country [20] 0 0
Belgium
State/province [20] 0 0
Wilrijk
Country [21] 0 0
Denmark
State/province [21] 0 0
Herlev
Country [22] 0 0
Finland
State/province [22] 0 0
Helsinki
Country [23] 0 0
France
State/province [23] 0 0
La Roche Sur Yon Cedex 9
Country [24] 0 0
France
State/province [24] 0 0
Lyon
Country [25] 0 0
France
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Marseille
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France
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Montpellier Cedex 5
Country [27] 0 0
France
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Paris Cedex 20
Country [28] 0 0
France
State/province [28] 0 0
Paris Cedex 5
Country [29] 0 0
France
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Toulouse Cedex
Country [30] 0 0
France
State/province [30] 0 0
Vandoeuvre les Nancy
Country [31] 0 0
Hungary
State/province [31] 0 0
Gyula
Country [32] 0 0
Hungary
State/province [32] 0 0
Kaposvar
Country [33] 0 0
Hungary
State/province [33] 0 0
Szombathely
Country [34] 0 0
Hungary
State/province [34] 0 0
Veszprem
Country [35] 0 0
India
State/province [35] 0 0
Karnataka
Country [36] 0 0
India
State/province [36] 0 0
Maharashtra
Country [37] 0 0
India
State/province [37] 0 0
Rajasthan
Country [38] 0 0
Netherlands
State/province [38] 0 0
Maastricht
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Poland
State/province [39] 0 0
Gdansk
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Poland
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Lubin
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Poland
State/province [41] 0 0
Poznan
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Poland
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Warszawa
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Poland
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Wroclaw
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Spain
State/province [44] 0 0
AndalucÃ-a
Country [45] 0 0
Spain
State/province [45] 0 0
Cataluña
Country [46] 0 0
Spain
State/province [46] 0 0
Galicia
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Guildford
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United Kingdom
State/province [49] 0 0
Leicester
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United Kingdom
State/province [50] 0 0
London
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United Kingdom
State/province [51] 0 0
Manchester
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Northwood
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00511459
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00511459