A multicenter, open label study to assess the effect of trastuzumab + Whole Brain Radiotherapy (WBRT) on brain metastases from HER-2 positive breast cancer. - bHERt2
- Conditions
- Stage IV, HER-2 positive breast cancer patients with brain metastasis and who are eligible for WBRT.MedDRA version: 13.1Level: PTClassification code 10006202Term: Breast cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2010-021191-29-IT
- Lead Sponsor
- ROCHE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
1. Written informed consent;
2. Patients aged = 18 years;
3. Able to comply with the protocol procedures;
4. Patients with prior histological and/or cytological diagnosis of
breast carcinoma with HER-2 over expression (IHC 3+; IHC 2+
and amplified FISH or CISH or SISH) who have first evidence of
disease progression to the brain, regardless of control of
extracranial disease if present;
5. At least one measurable brain metastasis evaluated with brain
contrast MRI;
6. Patients for whom, according to investigator assessment, WBRT
is the best therapeutic option;
7. Symptomatic brain lesions and/or brain lesions as the only site
of metastatic disease and/or controlled extra-cerebral disease
with brain metastases;
8. Patients are eligible regardless of the type and number of prior
or concomitant trastuzumab-based therapies received. Patients
who received trastuzumab in the adjuvant setting can be
included in the study; 9. Performance Status (WHO) = 2;
10. Left ventricular ejection fraction (LVEF) = 50% at baseline
(assessed within 2 weeks prior to ICF signature ) as determined
by either 2D echocardiogram (ECHO) or MUGA;
11. Prior maximum cumulative dose of doxorubicin < 360 mg/m2 or
maximum cumulative dose of epirubicin < 720 mg/m2 or
equivalent.
12. Life expectancy = 3 months;
13. Adequate haematological function:
- Absolute neutrophils count (ANC) = 1.5 x 109/L AND
- Platelet count = 100 x 109/L AND
- Hemoglobin = 9 g/dL
14. Adequate liver function:
- Total bilirubin < 1.5 x upper limit of normal (ULN) AND
- Aspartate aminotransferase (AST), alanine aminotransferase
(ALT) < 5 x ULN;
15. Adequate renal function:
- Serum creatinine = 1.5 mg/dL
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Presence of neoplastic meningitis;
2. Any prior radiotherapy to the brain;
3. Patients with non-controlled extra-cerebral disease who at the
time of enrolment, according to investigator judgment, are
eligible to a chemotherapy treatment not compatible with the
study protocol related timelines;
4. Patients for whom, according to investigator assessment,
stereotactic radiotherapy is the best therapeutic option;
5. Previous neoplasm, other than breast carcinoma, within 5 years
since the enrolment. Patients with previous diagnosis of in situ
carcinoma of the cervix and/or non-melanoma carcinomatous
lesions of the skin can be included into the study;
4. Uncontrolled claustrophobia;
5. Uncontrolled hypertension (systolic > 180 mmHg and/or
diastolic > 100 mmHg);
6. Clinically significant (i.e. active) cardiovascular disease, e.g.
cerebrovascular accident (CVA) and myocardial infarction (= 6
months before enrollment), unstable angina, congestive heart
failure NYHA class = II, serious cardiac arrhythmia requiring
medication during the study which might interfere with
regularity of the study treatment, or not controlled by
medication;
7. Pregnant or lactating females;
8. For women of childbearing potential (women < 2 years after last
menstruation) not able or willing to use an effective form of
contraception (patient and/or partner, e.g., surgical sterilization,
a reliable barrier method, birth control pills, or contraceptive
hormone implants) and to continue its use for the duration of
study treatment and for 6 months after the last dose of study
treatment;
9. Known hyper-sensitivity to trastuzumab and any of its excipients or any other contraindications to treatment with
trastuzumab;
10. Evidence of ongoing or active infection, any other disease,
neurological, endocrine, pulmonary, hepatic or metabolic
dysfunction; physical examination finding or laboratory finding
giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or puts the
patient at high risk for treatment-related complications;
11. Treatment with any other investigational agent, or participation
in another clinical trial within 28 days prior to enrollment.
12. High steroids dose (equivalent to dexamethasone > 16 mg/day).
13. Treatment with chemotherapy and/or lapatinib within 2 weeks
prior to ICF signature.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the brain response rate to trastuzumab + WBRT in HER-2 positive breast cancer patients with brain metastases and who are eligible for WBRT (cycle 7).;Secondary Objective: 1. To evaluate brain progression rate at cycle 15 2. To evaluate brain progression free survival (B-PFS) 3. To determine patients’ survival status at the end of the study 4. To evaluate tolerability and safety;Primary end point(s): The primary efficacy endpoint is the brain objective response rate measured at cycle 7.
- Secondary Outcome Measures
Name Time Method