A multicenter single arm study of trastuzumab emtansine (T-DM1) in Her2 positive locally advanced or metastatic breast cancer patients who have received prior anti-Her2 and chemotherapy-based treatment.
1. HER2-positive disease determined locally i.e., immunohistochemistry (IHC) 3 + and/or
gene-amplified by in-situ hybridisation (ISH) as per institutional practice (however, both
tests should be performed wherever possible and only one positive result is required
for eligibility)
2. Histologically or cytologically confirmed invasive breast cancer (BC)
3. Prior treatment for BC in the adjuvant, unresectable, locally advanced or metastatic
setting must include both chemotherapy, alone or in combination with another agent, hormonal therapy is allowed)
4. Documented progression of incurable, unresectable, locally advanced, or metastatic
breast cancer (mBC), defined by the investigator: progression must occur during or
after most recent treatment for locally advanced/mBC or within 6 months of completing
adjuvant therapy
5. Measurable and/or non-measurable disease
6. Signed written informed consent approved by the institution’s independent Ethical
Committee (EC)
7. Age ≥ 18 years
8. Left ventricular ejection fraction (LVEF) ≥ 50% by either echocardiogram (ECHO) or
multiple-gated acquisition scan (MUGA)
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
10. Adequate organ function:
•Absolute neutrophil count >1500 cells/mm3
•Platelet count >100,000 cells/mm3
•Hemoglobin > 9.0 g/dL. Patients are allowed to be transfused red blood cells to this
level
•Albumin ≥ 2.5 g/dL
•Total bilirubin ≤ 1.5 upper limit of normal (ULN) serum glutamic oxaloacetic
transaminase (SGOT) or AST, serum glutamic pyruvic transaminase (SGPT) or
ALT, and alkaline phosphatase ≤ 2.5 x ULN with the following exception: Patients
with bone metastases: alkaline phosphatase ≤ 5 x ULN
•Creatinine clearance > 50 mL/min based on Cockroft-Gault glomerular filtration rate
(GFR) estimation: (140 − Age) x (weight in kg) x (0.85 if female)/(72 x serum
creatinine)
•International normalized ratio (INR) and activated partial thromboplastin time (aPTT)
<1.5 x ULN (unless on therapeutic coagulation)
11. For women of childbearing potential and men with partners of childbearing potential
agreement by the patient and/or partner to use a highly effective non-hormonal form of
contraception such as surgical sterilization or two effective forms of non-hormonal
contraception
12. Negative serum pregnancy test for women of childbearing potential (including premenopausal
women who have had a tubal ligation) and for all women not meeting the
definition of postmenopausal ( ≥ 12 months of amenorrhea), and who have not
undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For
all other women, documentation must be present in medical history confirming that the
patient is not of childbearing potential.
1. History of treatment with trastuzumab emtansine
2. Prior enrollment into a clinical study containing trastuzumab emtansine regardless of
having received trastuzumab emtansine or not
3. Peripheral neuropathy of Grade ≥ 3 per NCI CTCAE Version 4.0
4. History of other malignancy within the previous 5 years, except for appropriately treated
carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer,
synchronous or previously diagnosed HER2-positive BC, or cancers with a similar
curative outcome as those mentioned above
5. History of receiving any anti-cancer drug/biologic or investigational treatment within 21
days prior to first study treatment except hormone therapy, which can be given up to 7
days prior to first study treatment; recovery of treatment-related toxicity consistent with
other eligibility criteria
6. History of exposure to the following cumulative doses of anthracyclines:
•Doxorubicin or liposomal doxorubicin > 500 mg/m2
•Epirubicin > 900 mg/m2
•Mitoxantrone >120 mg/m2
•If another anthracycline, or more than one anthracycline, has been used, the
cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.
7. History of radiation therapy within 14 days of first study treatment. The patient must
have recovered from any resulting acute toxicity (to Grade ≤ 1) prior to first study
treatment.
8. CNS only disease
9. Brain metastases which are symptomatic. NOTE: a 14 days window after end of
radiotherapy must be observed. Patient must not be receiving steroids to control
symptoms
10. History of a decrease in LVEF to < 40% or symptomatic CHF with previous
trastuzumab treatment
11. History of symptomatic congestive heart failure (CHF; New York Heart Association
[NYHA] Classes II−IV) or serious cardiac arrhythmia requiring treatment
12. History of myocardial infarction or unstable angina within 6 months of first study
treatment
13. Current dyspnea at rest due to complications of advanced malignancy or requirement
for continuous oxygen therapy
14. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular,
pulmonary, or metabolic disease)
15. Pregnancy or lactation
16. Currently known active infection with HIV, hepatitis B virus, or hepatitis C virus
17. History of intolerance (such as Grade 3−4 infusion reaction) or hypersensitivity to
trastuzumab or murine proteins
18. Assessed by the investigator to be unable or unwilling to comply with the requirements
of the protocol throughout
Centre Hospitalier de Luxembourg
Myriam Alexandre & Céline Vidaillac
myriam.alexandre@crp-sante.lu
+352 26 970 855 or +352 26 970 936
for articles/videos/studies
This page provides the list of clinical studies currently registered in the LuxCLIN platform in the different therapeutic areas. By clicking on each study title, more information is displayed concerning the study objective and the participation conditions.
