E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with inflammatory or locally advanced operable breast cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021980 |
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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 determine the rate of pathological complete responses (pCR) |
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E.2.2 | Secondary objectives of the trial |
- To determine the objective response rate (RR), disease-free interval (DFI), overall survival (OS), and rate of breast conservative surgery (BCS). - To evaluate the safety of this regimen. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients with histologically proven stage III, or inflammatory breast cancer Female patients >18 years ER/PgR positive or negative and HER-2 negative patients No treatment with previous chemotherapy/endocrine therapy Performance status 0-1 (ECOG scale) No evidence of distant metastatic disease No other primary tumors within the last 5 years prior to enrolment, except for adequately treated carcinoma in situ of the cervix or basal cell skin cancer. No significant concomitant illness such as diabetes, cardiovascular, renal, or neurological impairments Absence of psychiatric illness undermining a correct understanding of the treatment program WBC >3,000/mm3; Neutrophils >2,000/mm3; Platelets >100,000/mm3; Haemoglobin >9 g/dL AST, ALT, gamma-GT <2.5 x upper normal limit and bilirubin <1.5 mg/dl Urine dipstick of proteinuria <2+. Patients discovered to have >2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate <1 g of protein/24hr. Creatinine <140 µmol/l (1.6 mg/dl); if bordeline limit values, the creatinine clearance should be >60 ml/min (actual or calculated by Cockcroft-Gault method) The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR, or appropriate monitoring test is within therapeutic limits and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of enrolment. Patients not receiving anti coagulant medication must have an INR <1.5 and aPTT <1.5 x ULN within 7 days of enrolment. Normal left ventricular ejection fraction (LVEF) (evaluated by echocardiography or MUGA scan). The results must be above the upper limit of normal for the institution. Institutional Signed Written Informed Consent obtained |
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E.4 | Principal exclusion criteria |
Primary breast cancer with histology other than adenocarcinoma. Primary breast carcinoma with any stage other than III. Patients with other non-malignant uncontrolled systemic diseases that would preclude trial entry in the opinion of the investigator. History or evidence or inherited bleeding diathesis or coagulopathy with the risk of bleeding Chronic daily treatment with aspirin (>325 mg/day) or clopidogrel (>75 mg/day) Serious non-healing wound, peptic ulcer, or bone fracture Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to enrolment, or minor surgical procedures, within 24 hours prior to enrolment History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of enrolment Clinical grade greater than or equal to 2 peripheral neuropathy Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start. Patients who are receiving other investigational drugs |
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E.5 End points |
E.5.1 | Primary end point(s) |
Rate of pathological complete responses |
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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 | 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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | 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) | 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.8.5 | 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 | Information not present in EudraCT |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
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 |