A Randomized Phase II Study to Determine the Efficacy and Tolerability of Two Doses of Eribulin Plus Lapatinib in Trastuzumab Pre-treated Patients With HER2-positive Metastatic Breast Cancer (E-VITA)
- Written informed consent prior to beginning specific protocol procedures, including
expected cooperation of the patients for the treatment and follow-up, must be
obtained and documented according to the local regulatory requirements.
- Complete baseline documentation must be submitted via the web-based data collection
system MedCODES® to the GBG Forschungs GmbH.
- Histological confirmed carcinoma of the breast with over-expression of HER2 (IHC3+ or
FISH pos., according to current guidelines of AGO). Every effort should be made to
make paraffin embedded tissue or slides from the original tumor and/or from
metastatic tissue available for confirmation of diagnosis and additional
- Locally advanced or metastatic stage of disease not suitable for surgery or
- Patients must have either measurable or non-measurable target lesions according to
RECIST criteria. Complete staging work-up within 4 weeks prior to registration. All
patients must have chest X-ray (PA and lateral), abdominal ultrasound or CT scan or
MRI, and bone scan. In case of positive bone scan, bone X-ray is mandatory. Other
tests may be performed as clinically indicated.
- The following previous systemic treatments are eligible:
- Previous treatment with trastuzumab either as (neo)adjuvant treatment for early
breast cancer and/or first and/or second line treatment for metastatic breast
- adjuvant and up to 2 chemotherapy regimen for metastatic breast cancer,
- if previous chemotherapy regimen were anthracycline based, the maximum
cumulative dose of prior anthracycline therapy must not exceed 360 mg/m² for
doxorubicin and 720 mg/m² for epirubicin,
- adjuvant endocrine therapy,
- palliative endocrine treatments,
- treatment with bisphosphonates (adjuvant and/or palliative),
- at least 4 weeks since radiotherapy, with full recovery. The measurable disease
must be completely outside the radiation field or there must be pathologic proof
of progressive disease. 7. Age >18 years. 8. ECOG performance status 0-2. 9.
- Absolute neutrophil count ≥ 1500 cells/ul,
- hemoglobin ≥ 10.0 g/dL (hemoglobin <10.0 g/dL is acceptable if it is corrected
by growth factor or transfusion),
- platelet count ≥100,000 cells/ul,
- bilirubin <= 1.5x the upper limit of normal for the institution (ULN),
- elevation of transaminases and alkaline phosphatase < 2.5x ULN or <5x ULN for
patients with liver metastases,
- creatinine <= 1.5 x ULN or creatinine-clearance > 40 ml/min (according to
- negative pregnancy test (urine or serum) within 14 days prior to registration
for all women of childbearing potential. 10. Normal cardiac ejection function as
determined by cardiac ultrasound (LVEF above institutional normal range).
11. A female either of:
- Non-childbearing potential i.e., physiologically incapable of becoming pregnant
because of history of hysterectomy, bilateral oophorectomy (ovarectomy), bilateral
tubal ligation or postmenopausal status.
- Childbearing potential with a negative serum pregnancy test within 2 weeks prior to
registration, preferably as close to the first dose as possible, and agrees to use
adequate contraception. Acceptable contraceptive methods, when used consistently and
in accordance with both the product label and the instructions of the physician, are
- An intrauterine device with a documented failure rate of less than 1% per year.
- Vasectomized partner who is sterile prior to the female subject's entry and is
the sole sexual partner for that female.
- Complete abstinence from sexual intercourse for 14 days before exposure to
investigational product, through the dosing period, and for at least 21 days
after the last dose of investigational product.
- Double-barrier contraception (condom with spermicidal jelly, foam suppository,
or film; diaphragm with spermicide; or male condom and diaphragm with
spermicide). 12. Female patients who are lactating should discontinue nursing
prior to the first dose of study drug and should refrain from nursing throughout
the treatment period and for 14 days following the last dose of study drug.
13. Patients must be available and compliant for treatment and follow-up.
Patients registered on this trial must be treated and followed up at the
participating or a cooperating center.
- Known hypersensitivity reaction to the compounds or incorporated substances (e.g.
halichondrin B and/or halichondrin B chemical derivative).
- Patients who have received eribulin or lapatinib before.
- Concurrent immunotherapy or hormonal therapy (anti-hormonal, contraceptive and/or
replacement therapy). Bisphosphonates may be continued.
- Life expectancy of less than 3 months.
- Parenchymal brain metastases, unless adequately treated by neurosurgery,
radiotherapy, radiosurgery or a combination.
- Any ongoing toxicity from prior anti-cancer therapy that is grade >1 and/or that is
progressing in severity, except alopecia or for stable sensory neuropathy Grade 2.
- Known or suspected congestive heart failure (>NYHA I) and/or coronary heart disease,
angina pectoris requiring anti-anginal medication, previous history of myocardial
infarction, evidence of transmural infarction on ECG, un- or poorly controlled
arterial hypertension (i.e. BP >150/100 mmHg under treatment with two
antihypertensive drugs), rhythm abnormalities requiring permanent treatment,
clinically significant valvular heart disease.
- Currently active infection.
- History of other malignancies within the last 5 years which could affect the
diagnosis, assessment or prognosis of metastatic breast cancer.
- Malabsorption syndrome or insufficient gastrointestinal function, preexisting
diagnosis of ulcerative colitis.
- Concurrent treatment with other experimental drugs; participation in another clinical
trial with any investigational not marketed drug within 30 days prior to study entry.
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition
that could interfere with subject's safety, provision of informed consent, or
compliance to study procedures.