E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10006187 |
E.1.2 | Term | Breast cancer |
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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 pCR rate of AC followed by ixabepilone relative to the pCR rate for AC followed by paclitaxel in women with early stage HER-2 and ER negative breast cancer To estimate the pCR rate of AC followed by ixabepilone relative to the pCR rate for AC followed by paclitaxel in a biomarker-defined population based on the following pre-defined biomarker sets: beta-3 tubulin assessed by immunohistochemistry (IHC), CAPG assessed by mRNA, TACC3 assessed by mRNA, A set of 20 genes assessed by mRNA, A set of 26 genes assessed by mRNA. |
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E.2.2 | Secondary objectives of the trial |
For each of the predictive models based on pre-defined biomarker sets: -Estimate PPV, NPV, sensitivity & specificity -Define classification threshold Explore gene expression patterns for GTSE1, isoforms of beta-tubulin & Kallikreins 5, 6 & 10 & protein expression patterns for MDR1 that may be differentially predictive of pCR in AC followed by ixabepilone treatment arm vs AC followed by paclitaxel treatment arm Explore other gene expression patterns that may be differentially predictive of pCR in AC followed by ixabepilone treatment arm vs AC followed by paclitaxel treatment arm Estimate clinical objective response rates (complete & partial) of neoadjuvant AC followed by ixabepilone or AC followed by paclitaxel in subjects with early stage breast cancer Determine rate of breast conservation surgery achieved in each treatment arm Evaluate safety of neoadjuvant AC followed by ixabepilone in subjects with early stage breast cancer not expressing HER-2 & ER |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1/ Signed Written Informed Consent 2/ Target Population a) Histologically confirmed primary invasive adenocarcinoma of the breast. b) Tumors must be estrogen receptor (ER) negative and HER-2/neu expression negative, as determined by local hospital laboratory (IHC =< 2+ or FISH negative). c) No prior treatment (irradiation, chemotherapy, hormonal, immunotherapy or investigational, etc.) for breast cancer excluding therapy for DCIS. Subjects receiving hormone replacement therapy (HRT) are eligible if this therapy is discontinued at least 2 weeks before starting study therapy. d) Subjects who received radiotherapy for DCIS may enroll. e) Disease free of prior malignancy for >= 5 years with the exception of curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix. f) Karnofsky performance status (KPS) of 80 - 100. g) Accessible for treatment and follow-up. h) Baseline MUGA or echocardiogram scan with LVEF of >= 50%. i) Adequate recovery from recent surgery. At least one week must have elapsed from minor surgery (placement of venous access device or fine needle aspiration) and at least 4 weeks from major surgery. 3/ Laboratory Parameters a) Absolute neutrophil count (ANC) >= 1500/mm³ b) Total bilirubin =< 1.5 times the upper limit of normal (ULN). c) AST or ALT =< 2.5 times the upper limit of normal (ULN). d) Platelets >= 100,000/ mm3. e) Serum creatinine =< 1.5 x ULN or 24-hour creatinine clearance > 60 mL/min (measured or calculated by Cockcroft-Gault method). f) Normal PTT and either INR or PT < 1.5 x ULN. 4/ Women, at least 18 years of age |
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E.4 | Principal exclusion criteria |
1/ Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational drug. b) Women who are pregnant (including positive pregnancy test at enrollment or prior to study drug administration) or breastfeeding. 2/ Target Disease Exceptions a) Evidence of metastatic breast cancer following a standard tumor staging work-up. b) Evidence of inflammatory breast cancer. c) Evidence of baseline sensory or motor neuropathy. 3/ Medical History and Concurrent Diseases a) Known human immunodeficiency viral (HIV) infection. b) Serious intercurrent infections or non-malignant medical illnesses that are uncontrolled or the control of which may be jeopardized by this therapy. c) Psychiatric disorders or other conditions rendering the subject incapable of complying with the requirements of the protocol. d) Clinically significant history of cardiovascular disease (history of unstable angina, congestive heart failure, uncontrolled hypertension, myocardial infarction or valvular heart disease). e) Subjects unfit for breast and/or axillary surgery (complete fixation of tumor, skin infiltration, erythema of the breast, and/or ulceration). f) Current participation in another drug trial. g) Subjects who received prior anthracycline therapy. 4/ Known allergy to any of the study drugs or to agents containing Cremophor® EL. 5/ Prohibited Therapies and/or Medications a) Other concurrent anti-tumor, chemotherapy, hormonal therapy, immunotherapy regimens or radiation therapy, standard or investigational. b) The following medication must be discontinued 72 hours prior to initiation of AC therapy and be withheld during AC therapy: barbiturates, phenytoin, chloral hydrate, corticosteroids, succinylcholine, allopurinol, imipramine and phenothiazines. (See Protocol Section 5.5.1, for other prohibited medications prior to and during administration of ixabepilone or paclitaxel). 6/ Prisoners or subjects who are compulsorily detained |
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E.5 End points |
E.5.1 | Primary end point(s) |
Pathologic complete response (pCR) rate in the breast and axillary lymph nodes, independent of the presence of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) in the breast tissue |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | No |
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 | 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.8.5 | 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 | 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
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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 | 6 |
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 | 6 |