| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| 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 of the study is to determine the clinical benefit of the addition of bevacizumab to standard chemotherapy regimens for previously untreated metastatic breast cancer, as measured by PFS based on investigator tumor assessment, assessed in a parallel manner as follows:
• Determination of the clinical benefit, as measured by PFS based on investigator tumor assessment, of the addition of bevacizumab to taxane therapy (docetaxel or paclitaxel protein-bound particles [Abraxane] administered every 3 weeks) and anthracycline-based therapy, compared with these chemotherapies alone, in subjects who are receiving first-line therapy for locally recurrent or metastatic breast cancer
• Determination of the clinical benefit, as measured by PFS based on investigator tumor assessment, of the addition of bevacizumab to capecitabine therapy compared with capecitabine therapy alone, in subjects who are receiving first-line therapy for locally recurrent or metastatic breast cancer |
|
| E.2.2 | Secondary objectives of the trial |
• To determine the clinical benefit, as measured by ORR, 1-year SR, and OS of the addition of BV to standard chemotherapy, compared with chemotherapy alone
• To estimate the clinical benefit, as measured by PFS based on investigator tumor assessment, of the addition of BV to taxane chemotherapy (docetaxel or paclitaxel [Abraxane]administered every 3 weeks), compared with chemotherapy alone
• To estimate the clinical benefit, as measured by PFS based on investigator tumor assessment, of the addition of BV to anthracycline-based combination chemotherapy, compared with chemotherapy alone
• To evaluate the toxicity, as measured by selected adverse events, adverse events resulting in treatment discontinuation, and serious adverse events, of standard chemotherapy options with or without BV
• To determine the clinical benefit of the addition of BV to standard chemotherapy regimens for previously untreated metastatic breast cancer, as measured by an PFS based on IRC data |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Histologically or cytologically confirmed adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease Locally recurrent disease must not be amenable to resection with curative intent.
• Signed Informed Consent Form
• Age >= 18 years
• For women of childbearing potential, use of accepted and effective method of non-hormonal contraception
• ECOG performance status of 0 or 1 (see Appendix B)
• Ability and capacity to comply with study and follow up procedures
• For anthracycline cohort only: adequate left ventricular function at study entry, defined as an LVEF >= 50% by either MUGA scan or ECHO.
• For subjects who have received recent radiation therapy: recovery prior to Day 0 from any significant (Grade >= 3) acute toxicity |
|
| E.4 | Principal exclusion criteria |
Disease and Treatment History
• Unknown HER2 status or known HER2-positive status
In general, HER2-positive status will be identified by a fluorescence in-situ hybridization (FISH) assay as evaluated at the institution, or, if FISH is unavailable, a 2+ or 3+ immunohistochemistry result (but method of identification may vary by region or institution). Subjects who have unknown HER2 status, and for whom determination of HER2 status is not possible, are eligible for this study.
HER2-positive subjects are eligible only if they have received prior treatment with Herceptin, unless Herceptin therapy is contraindicated or unavailable (applicable only for certain ex-U.S. sites that have not yet approved this therapy).
•Prior chemotherapy for locally recurrent or metastatic disease
•Prior hormonal therapy less than 1 week prior to Day 0.
Prior hormonal therapy for locally recurrent or metastatic disease is allowed.
•Prior adjuvant or neoadjuvant chemotherapy within 12 months prior to Day 0
•For anthracycline cohort only: prior anthracycline as part of neoadjuvant or adjuvant therapy for localized breast cancer
•Investigational therapy within 28 days of Day 0
•Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study
•Prior therapy with bevacizumab, sorafenib, sunitinib, or other VEGF pathway-targeted therapy
•Minor surgical procedures, such as fine needle aspirations or core biopsies, within 7 days prior to Day 0 Bevacizumab Exclusion Criteria
•Known brain or other CNS metastases
•Blood pressure of > 150/100 mmHg
•Unstable angina
•New York Heart Association (NYHA) Grade II or greater CHF (see Appendix D)
•History of myocardial infarction within 6 months prior to Day 0 •History of stroke or transient ischemic attack within 6 months prior to Day 0 •Clinically significant peripheral vascular disease
•Evidence of bleeding diathesis or coagulopathy
•History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
•History of anaphylactic reaction to monoclonal antibody therapy not controlled with treatment premedication
•Serious non-healing wound, ulcer, or bone fracture Fractures secondary to metastatic disease may be allowed if stable and surgery (if applicable) is completed ≥28 days prior to Day 0
General Exclusion Criteria
•Pregnancy (positive serum pregnancy test) or lactation
•Inadequate organ function, as evidenced by any of the following laboratory values: Absolute neutrophil count < 1500/mcgL
Platelet count < 100,000/mcgL
Total bilirubin > 1.5 mg/dL AST, and/or ALT > 2 x upper limit of normal (> 5x ULN in subjects with known liver involvement)
Alkaline phosphatase >2 x ULN (>5xULN in subjects with known liver involvement and >7xULN in subjects with known bone involvement)
Serum creatinine > 2.0 mg/dL
PTT and/or either INR or PT > 1.5x upper limit of normal (except for subjects receiving anti-coagulation therapy)
Urine protein/creatinine ratio > 1.0 at screening for U.S. subjects (see Appendix C), or urine dipstick for proteinuria >= 1+ at screening followed by 24-hour urine collection demonstrating > 1 g protein/24 hr for ex-U.S. subjects
•Uncontrolled serious medical or psychiatric illness
•Active infection requiring IV antibiotics at Day 0
•History of other malignancies within 5 years of Day 0 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix Subjects with a history of bilateral breast cancer or previous history of breast cancer will be eligible. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| 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 | Yes |
| 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
|
|
| 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 | 9 |
| 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 | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
