E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally recurrent or metastatic breast cancer |
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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 | 10006279 |
E.1.2 | Term | Breast neoplasm |
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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 estimate the response rate of ixabepilone/bevacizumab combination in each of the following 2 schedules relative to the reference arm of paclitaxel plus bevacizumab: Ixabepilone administered every week for 3 weeks followed by 1 week rest plus bevacizumab administered every 2 weeks (Arm A) and Ixabepilone administered every 3 weeks plus bevacizumab administered every 3 weeks (Arm B). |
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E.2.2 | Secondary objectives of the trial |
To determine the week 24 PFS rate To estimate the progression free survival for the 3 treatment arms To determine time to response for the 3 treatment arms To determine the duration of response for the 3 treatment arms To estimate overall survival for the 3 treatment arms Determine the safety and tolerability of these schedules in this subject population for the 3 treatment arms |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Men or women ages >18 years Histologic or cytologic confirmed diagnosis of invasive adenocarcinoma originating in the breast with evidence of locally recurrent or metastatic disease. At least one target lesion per RECIST criteria (Section 3.3). Locally recurrent disease must not be amenable to resection with curative intent. Previously radiated area(s) must not be the only site of disease. Subjects must not have received cytotoxic chemotherapy for locally recurrent/metastatic disease. (Subjects may have received adjuvant or neo adjuvant chemotherapy) Subject who received prior adjuvant or neoadjuvant taxane therapy must have relapsed 12 months after completing therapy. Subjects must not have breast cancer known to over express or amplify Her-2 (i.e., 3+ by immunohistochemistry and/or FISH positive). Prior hormonal therapy in adjuvant, recurrent or metastatic setting is allowed, but this must have been discontinued at least 2 weeks prior to randomization. Karnofsky performance status (PS) of 80-100 (or ECOG, PS of 0-1). Estimated life expectancy of at least 12 weeks. Recovery (except for alopecia) from recent therapy, including chemotherapy, immunotherapy, biological therapy or investigational product. Any such therapy must have been completed at least 3 weeks prior to randomization and at least 6 weeks from use of nitrosourea, or mitomycin. Recovery from recent surgery and radiation therapy. At least one week must have elapsed from minor surgery (e.g. placement of venous access device or fine needle aspiration) and/or focal/palliative radiation therapy; at least 3 weeks from radiation and at least 4 weeks from major surgery. |
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E.4 | Principal exclusion criteria |
WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 8 weeks after treatment withdrawal. Women who are pregnant or breastfeeding Women with a positive pregnancy test on enrollment or prior to study drug administration. Evidence of baseline sensory or motor neuropathy. Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled or the control of which may be jeopardized by this therapy. History of abdominal fistula, GI perforation, intra-abdominal abscess, or serious gastric ulcer or bone fracture within 6 months prior to study entry. Clinically significant cardiovascular disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension (>150/90), myocardial infarction or cerebral vascular accidents) within 6 months prior to study entry. Prior history of high dose chemotherapy with bone marrow transplant or peripheral blood stem cell transplant within the previous 2 years. Prior treatment with an epothilone (or epothilone analogue) or bevacizumab. History of bleeding diathesis, pulmonary embolism, deep vein thrombosis or use of therapeutic anticoagulants as therapy. (Low dose anticoagulant therapy to maintain vascular access is allowed) Concurrent non-healing wound or fracture. Any current or previous history of brain and/or leptomeningeal metastases including evidence of cerebral edema by computerized tomography (CT) or magnetic resonance imaging (MRI). Head CT or MRI must be obtained within 4 weeks prior to randomization |
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E.5 End points |
E.5.1 | Primary end point(s) |
To estimate the response rate of ixabepilone/bevacizumab combination in each of the following 2 schedules relative to the reference arm of paclitaxel plus bevacizumab: Ixabepilone administered every week for 3 weeks followed by 1 week rest plus bevacizumab administered every 2 weeks (Arm A) and Ixabepilone administered every 3 weeks plus bevacizumab administered every 3 weeks (Arm B). |
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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 | 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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
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 |
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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
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Off study visit procedures should be completed within 30 days after the last dose of study drug. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | |
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 | 8 |