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 | 10021944 |
E.1.2 | Term | Infiltrating ductal 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 assess the efficacy and safety of the multi-targeted signal transduction inhibitor, sunitinib (Sutent®) in conjunction with aromatase inhibitor, exemestane (Aromasin®) as neoadjuvant therapy for menopausal women diagnosed with breast cancer and the primary end-point will be Ki67 response to therapy. |
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E.2.2 | Secondary objectives of the trial |
-Clinical Response Rate (cRR) -Radiological response rate (rRR) -Clinical/radiological response among patients over-expressing EGFR/HER-2. -Complete pathological response (pCR) -Circulatory endothelial cells (CEC) and circulatory endothelial progenitor (CEP) levels pre, during and post treatment. -Analysis of candidate genes and global gene expression profiling to identify molecular markers of response or resistance. -Disease free and overall survival
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
ARTiST-SCIENCE sub-study: Tumour tissue samples from paraffin-embedded blocks obtained at initial diagnosis and surgery, will be analysed. Analysis of tumour tissue will involve (i) tissue microarrays for immunohistochemistry (IHC) of protein gene products and in situ hybridisation analysis, and (ii) whole-genome profiling using expression and DNA microarrays.
CTCR-BR06 sub-study Fresh tumour tissue samples will also be collected before, during, and after neoadjuvant therapy. Analysis of tumour tissue will involve assessment of prospective predictive high throughput molecular profiling, with candidate gene and mutational analysis.
Optional Imaging sub-study : In some specific centres, patients will be invited to take part in an optional imaging sub-study involving DCE-MRI and CT-PET scans.
DETECT-2 sub-study ( to start at a later date) Blood samples will be collected on several occasions. Isolation, enumeration, characterization of the molecular profile of CEC/CEPs tissue and change in CEC/CEPs levels in response to therapy.
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E.3 | Principal inclusion criteria |
Key Inclusion criteria -Ultrasound Size: greater than 1 cm. -Diagnosis of invasive breast cancer on core biopsy. -Patients with localised or locally advanced invasive breast cancer. -Histological grade : G1-3. -ER positive (Allred ≥ 4).
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E.4 | Principal exclusion criteria |
Key Exclusion criteria:
- Previous history of cancer, excluding basal cell carcinoma or cervical carcinoma in-situ. - Previous deep vein thrombosis or pulmonary embolism. - Uncontrolled hypertension. -Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack. -Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication. -Ongoing cardiac dysrhythmias of ≥ grade 2 (NCI CTCAE grading version 3.0), atrial fibrillation of any grade, or prolongation of the QTc interval >470 msec. -Treatment with terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, ketoconazole or indapamide - Known human immunodeficiency virus (HIV) positive, or acquired immunodeficiency syndrome (AIDS) related illness. - Osteoporosis
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E.5 End points |
E.5.1 | Primary end point(s) |
Ki67 response to therapy.
The principal measure we will use to assess the success of the treatment is a marker called Ki67, which measures the rate at which cancer cells divide. This is the primary end-point of the trial. |
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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 | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | 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 | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
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 | 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
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When the study report is published. |
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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 | 5 |
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 | 5 |
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 |