| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Tratamiento de pacientes con cáncer de mama localmente recurrente o metastásico HER2- positivo que no han recibido previamente quimioterapia para enfermedad localmente recurrente o metastásica.
HER2-positive locally recurrent or metastatic breast cancer. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027475 |
| E.1.2 | Term | Metastatic breast cancer |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10065430 |
| E.1.2 | Term | HER-2 positive breast cancer |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10006198 |
| E.1.2 | Term | Breast cancer recurrent |
|
| 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 |
| The primary objective is to evaluate the overall response rate (ORR) in patients with HER2-positive locally advanced or metastatic breast cancer receiving bevacizumab, trastuzumab and capecitabine as first-line treatment for metastatic disease. |
|
| E.2.2 | Secondary objectives of the trial |
Secondary objectives are to evaluate:
- Progression-Free Survival (PFS)
- Overall Survival (OS)
- Time to Progression (TTP)
- Safety and tolerability |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age > 18 years.
2. Histologically or cytologically confirmed breast adenocarcinoma with measurable
(per RECIST), locally recurrent or metastatic lesions.
3. Candidates for Xeloda based chemotherapy. Locally advanced disease must not be amenable to resection with curative intent.
4. Documented HER2 positive disease (HER2 overexpression indicated by IHC 3+
and/or FISH + and/or chromogenic in situ hybridization (CISH) + of the primary
tumor or a metastasis).
5. Documented ER/PgR status (positive or negative).
6. ECOG Performance Status ? 2.
7. Able and willing to comply with the protocol.
8. Written and signed informed consent prior to beginning study-specific procedures
showing the patient?s awareness and willingness to participate in the trial and
comply with its proceedings and with the understanding that the patient has the
right to withdraw from the study at any time without prejudice. (Note: the
informed consent document must be approved by the institution?s Independent
Ethics Committee). |
|
| E.4 | Principal exclusion criteria |
1. Previous treatment for locally advanced or mBC other than hormone therapy or
radiotherapy. Anti-epidermal growth factor receptor or anti-HER2 agents or
vaccines and cytotoxic chemotherapies for locally recurrent or mBC are not
allowed. Patients must have fully recovered from side effects of any prior
radiotherapy.
2. Any prior neoadjuvant or adjuvant treatment with anthracyclines completed less
than 6 months prior to enrolment. The max. cumulative dose received must not
have exceeded 360 mg/sqm for doxorubicin or 720 mg/sqm for epirubicin.
3. Chronic daily treatment with corticosteroids and/or with aspirin or clopidogrel.
4. Requirement for concurrent use of the antiviral agent sorivudine, or chemically
related analogues, such as brivudine.
5. Minor surgical procedures, within 24 hours prior to enrolment.
6. Current or recent (within the 30 days prior to starting study treatment)
treatment with another investigational drug or participation in another
investigational study.
7. Inadequate bone marrow function, liver function and or renal function
8. Patients not receiving anticoagulant medication who have an International
Normalized Ratio (INR) > 1.5 or an activated partial thromboplastin time (aPTT) >
1.5 x ULN within 7 days prior to enrolment.
? Note: Patients receiving full dose oral or parenteral anticoagulants may be included as long as anticoagulant dosing has been stable for at least two weeks prior to study entry and the appropriate coagulation monitoring tests are within therapeutic limits.
9. Other primary malignancy (including primary brain tumors) within the last 5 years
prior to enrolment, except for adequately treated carcinoma in situ of the cervix,
squamous carcinoma of the skin, or adequately controlled limited basal cell skin
cancer.
10. Dyspnea at rest due to complications of advanced malignancy (e.g. pulmonary
metastases with lymphangitis) or any condition necessitating supportive oxygen
therapy.
11. Evidence of CNS metastasis.
12. Evidence of spinal cord compression caused by metastases.
13. History or evidence upon physical/neurological examination of CNS disease
unrelated to cancer (e.g. uncontrolled seizures) unless adequately treated with
standard medical therapy.
14. Major surgical procedure, open biopsy or significant traumatic injury within 28
days prior to enrolment, or anticipation of the need for major surgery during the
course of the study treatment.
15. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg)
or clinically significant (i.e. active) cardiovascular disease
16. Baseline LVEF < 50% measured by either echocardiography or MUGA.
17. History or evidence of inherited bleeding diathesis or coagulopathy with the risk
of bleeding.
18. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months of enrolment.
19. Active infection requiring IV antibiotics at enrolment.
20. Serious non-healing wound, peptic ulcer, or bone fracture.
21. Clinically significant malabsorption syndrome, or inability to take oral medication.
22. Evidence of any other disease, metabolic or psychological dysfunction, physical
examination finding, or clinical laboratory finding giving reasonable suspicion of a
disease or condition that contraindicates the use of an investigational drug, may
affect patient compliance with study routines, or place the patient at high risk
from treatment related complications.
23. Known hypersensitivity to any of the study drugs or excipients.
24. History of severe and unexpected reactions to fluoropyrimidine therapy or with
known hypersensitivity to fluorouracil.
25. Known dihydropyrimidine dehydrogenase deficiency.
26. Pregnant or lactating females.
27. Fertile males or females of childbearing potential (<2 years after last
menstruation) unwilling or unable to use effective non-hormonal means of
contraception
28. Life expectancy ? 12 weeks. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint is ORR defined as the percentage of patients with CR or PR, as assessed by RECIST. |
|
| 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 | No |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| 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 | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 55 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| 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
|
| The study will end when the ITT study population death rate exceeds 80%. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| 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 | 3 |
| 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 |
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