E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post menopausal women with hormone (ER/PgR) receptor positive breast cancer |
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E.1.1.1 | Medical condition in easily understood language |
Post menopausal women with hormone (ER/PgR) receptor positive breast cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
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 |
To determine whether perioperative endocrine therapy with an aromatase inhibitor (AI) for two weeks before and after surgery (perioperative therapy) followed by standard adjuvant therapy improves outcome compared with standard therapy alone in postmenopausal women with hormone receptor positive breast cancer.
To determine whether the proliferation marker Ki67 as measured by immunohistochemistry (IHC) in the excised cancer around 2 weeks after starting AI therapy will predict for relapse free survival (RFS) more effectively than the pre-treatment Ki67 value in the individual patient as suggested in a clinical pilot study.
To determine whether molecular profiling 2 weeks after starting endocrine therapy predicts for long-term outcome in postmenopausal women with hormone receptor positive breast cancer better than in untreated patients.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Hormone receptor positive breast cancer is defined as an Allred score of 3 or more, or a Histoscore of 2 or more, or more than 1% of positive cells for oestrogen receptor or progesterone receptor.
1) Post menopausal women with core biopsy-proven hormone receptor positive invasive breast cancer. Postmenopausal is defined as a woman aged ≥50 years fulfilling any one of the following criteria: i) aged >50 years with amenorrhoea >12 months and an intact uterus; ii) has undergone a bilateral oophorectomy; iii) in women who have undergone a hysterectomy, then FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged <55 years; or iv) in women who have been on HRT within the last 12 months and therefore not amenorrhoeic, FSH levels within the postmenopausal range (utilising ranges from the testing laboratory facility) are required if the patient is aged <55 years. 2) No evidence of metastatic spread by standard assessment according to local guidelines 3) Standard adjuvant endocrine therapy indicated 4) A palpable tumour of any size , or a tumour with an ultrasound size of at least 1.5cm 5) WHO performance status of 0, 1, or 2 6) Written informed consent to participate in the trial and to donation of tissue (fresh tissue and surplus tissue from diagnostic procedures) and blood samples.
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E.4 | Principal exclusion criteria |
1) Locally advanced/inoperable breast cancer 2) Evidence of metastatic disease 3) Previous invasive breast cancer or bilateral breast cancer (surgically treated DCIS or LCIS allowed) 4) Concurrent use (defined as use within 4 weeks prior to baseline tissue sample being taken prior to entry) of HRT or any other oestrogen-containing medication (including vaginal oestrogens) 5) Previous use of oestrogen implants at ANY time 6) Prior endocrine therapy or chemotherapy for breast cancer 7) Any invasive malignancy diagnosed within previous 5 years (other than basal cell carcinoma or cervical carcinoma in situ) 8) Any severe co-incident medical disease, inability to give informed consent or unavailability for follow-up 9) Treatment with an unlicensed or investigational drug within 4 weeks before randomisation 10) Continuous long term systemic steroid usage |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary clinical analysis will be conducted after a median follow-up of five years or sufficient events have been observed to satisfy the primary analysis as determined by the IDMC. |
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E.5.2 | Secondary end point(s) |
• Time to local recurrence; • Time to distant recurrence; • Overall survival; • Breast cancer free survival; • Proliferation rate (Ki67) at baseline core biopsy, and at surgical excision (biological endpoint) ; and • Gene expression profile at core biopsy and at surgical excision.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The primary clinical analysis will be conducted after a median follow-up of five years or sufficient events have been observed to satisfy the primary analysis as determined by the IDMC. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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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 | 100 |
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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For the purposes of Clinical Trial Authorisation (CTA) under the European Union Directive 2001/20/EC, the study is deemed to have ended 30 days after the last patient receives the last dose of the investigational medicinal product (IMP). |
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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 | 3 |
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 | 3 |
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 |