E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IV, HER-2 positive breast cancer patients with brain metastasis and who are eligible for WBRT. |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006202 |
E.1.2 | Term | Breast cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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). |
|
E.2.2 | Secondary objectives of the trial |
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 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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 |
|
E.4 | Principal exclusion criteria |
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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the brain objective response rate measured at cycle 7. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
Lo studio terminera` al decesso di tutti i pazienti o 4 settimane dopo l`ultima somministarzione di farmaco, quale evento si verifichi per primo. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |