RANDOMIZED, PLACEBO-CONTROLLED,DOUBLE-BLIND PHASE 1B/2 STUDY OF U3-1287(AMG 888) IN COMBINATION WITHTRASTUZUMAB PLUS PACLITAXEL IN NEWLYDIAGNOSED HER2-POSITIVE METASTATICBREAST CANCER (MBC)

Not Applicable

Conditions: -C50 Malignant neoplasm of breast
Malignant neoplasm of breast
C50

Registration Number: PER-021-13

Lead Sponsor: DAIICHI SANKYO PHARMA DEVELOPMENT,

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Sex: Female

Target Recruitment: 0

Inclusion Criteria

Subjects must satisfy all of the following criteria to be
included in the study:
1. Women ≥ 18 years old.
2. Histologically or cytologically confirmed
adenocarcinoma of the breast with metastatic
disease and at least 1 measureable lesion per
RECIST guidelines Version 1.1.
3. Documented HER2+ disease as measured by
fluorescence in situ hybridization (FISH) or
immunohistochemistry (IHC) (3+).
4. Eastern Cooperative Oncology Group (ECOG)
performance status 0 or 1.
5. Hematological function, as follows:
-Absolute neutrophil count (ANC) ≥ 1.5 x
10^9/L
- Platelet count ≥ 100 x 10^9/L
- Hemoglobin ≥ 9 g/dL.
6. Renal function, as follows:
- Calculated creatinine clearance
≥ 60 mL/min using the modified
Cockroft-Gault equation.
7. Hepatic function, as follows:
- Aspartate aminotransferase (AST)
≤ 2.5 x the upper limit of normal (ULN) (if
liver metastases are present, < 5 x ULN)
- Alanine aminotransferase (ALT)
≤ 2.5 x ULN (if liver metastases are present,
< 5 x ULN)
- Alkaline phosphatase ≤ 2.0 x ULN (if bone
or liver metastases are present, < 5 x ULN)
- Bilirubin ≤ 1.5 x ULN.
8. Prothrombin time (PT) and partial thromboplastin
time (PTT) ≤ 1.5 x ULN.
9. Availability of archived tumor sample or fresh
tumor specimen (does not have to be provided by
treatment start) to confirm HER2 status and for
tumor biomarkers/mutation analysis.
10. Subjects must be postmenopausal (no menstrual
period for a minimum of 12 months) or surgically
sterile, or must use maximally effective birth
control during the period of therapy, and be willing
to use contraception for 6 months following the last
investigational drug dose and have a negative urine
or serum pregnancy test upon entry into this study if
subject is of childbearing potential. Partners of
subjects must be surgically sterile or willing to use a
double barrier contraception method upon
enrollment, during the course of the study, and for
6 months after the last investigational drug dose
received.
11. Subjects must be willing and able to comply with
scheduled visits, treatment plan, laboratory tests,
and other study procedures.
12. Subjects must be competent and able to
comprehend, sign, and date an Independent Ethics
Committee (IEC)- or Institutional Review Board
(IRB)-approved informed consent form (ICF)
before performance of any study-specific
procedures or tests.

Exclusion Criteria

Subjects who meet any of the following criteria will be
disqualified from entering the study:
1. Prior treatment for metastatic disease other than
radiation therapy. Neoadjuvant/adjuvant therapy with paclitaxel, and/or docetaxel, and/or
trastuzumab is allowed if completed more than 12
months prior to relapse/progression.
2. Clinically active brain metastases, defined as
untreated symptomatic, or requiring therapy with
steroids or anticonvulsants to control associated
symptoms. Subjects with treated brain metastases
that are no longer symptomatic and require no
treatment with steroids or anticonvulsants may be
included in the study if they have recovered from
the acute toxic effect of radiotherapy.
3. Left ventricular ejection fraction (LVEF) < 50%.
History of LVEF decline to < 50% on prior
trastuzumab therapy.
4. Therapeutic or palliative radiation therapy or major
surgery within 4 weeks before study drug treatment.
5. History of other malignancies, except adequately
treated nonmelanoma skin cancer, curatively treated
in-situ cancer, or other solid tumors curatively
treated with no evidence of disease for ≥ 5 years.
6. Uncontrolled hypertension (diastolic blood pressure
> 100 mmHg or systolic blood pressure
> 140 mmHg). Use of antihypertensive
medications is permissible to maintain blood
pressure within the required parameters.
7. Clinically significant electrocardiogram (ECG)
changes that obscure the ability to assess the RR,
PR, QT, QTc and QRS intervals. Subjects with left
bundle branch block, atrial fibrillation and use of a
cardiac pacemaker specifically will be excluded.
8. Ascites or pleural effusion requiring chronic
medical intervention.
9. Pre-existing peripheral neuropathy > grade 1.
10. Myocardial infarction, symptomatic congestive
heart failure (CHF) (New York Heart Association
> Class II), unstable angina, or unstable cardiac
arrhythmia requiring medication within 1 year
before enrollment.
11. Use of cytochrome P450 (CYP) 3A4 (CYP3A4) or
CYP2C8 inducers within 28 days prior to Day 1,
use of CYP3A4 or CYP2C8 inhibitors within 14 days prior to Day 1, or concurrent use of CYP3A4 or CYP2C8 inducers or inhibitors.
12. Use of amiodarone within 6 months prior to
enrollment.
13. Concurrent use of antiarrhythmic medications.
14. Participated in clinical drug studies within 4 weeks
(2 weeks for small molecule tyrosine kinase
inhibitors; 6 weeks for mitomycin C and
nitrosoureas) before study drug treatment. Current
participation in other investigational protocols or
procedures.
15. Uncontrolled infection requiring IV antibiotics,
antivirals, or antifungals.
16. Known human immunodeficiency virus (HIV)
infection, or active hepatitis B or C infection.
17. History of hypersensitivity to any of the study drugs
or to any excipients.
18. Serious intercurrent medical or psychiatric illnesses
or any other conditions that in the opinion of the
Investigator would impair the ability to give
informed consent or unacceptably reduce protocol
compliance or safety of the study treatment.
19. Pregnant, breastfeeding, or unwilling/unable to use
acceptable contraception.
20. QTc interval > 450 msec by Friderica’s formula on
two successive screening measurements (second
measu

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method