E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal early breast cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 whether the addition of a COX2 inhibitor to an aromatase inhibitor results in greater objective clinical response, with acceptable toxicity, than an aromatase inhibitor alone. Primary endpoint is objective clinical response (Complete Response, Partial Response) during neoadjuvant treatment.
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints include:
-Objective ultrasound-determined response (Complete Response, Partial Response) during neoadjuvant treatment -Type of surgery -Axillary lymph node involvement at surgery -Biological profiling for prognostic and predictive indictors -Local recurrence -Progression-free survival -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 |
TRANS NEO-EXCEL: Translational science substudy is an optional substudy (same version and date as main protocol (Version 3.0: 25th September 2009) ). Objective: Biological profiling for prognostic and predictive indictors |
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E.3 | Principal inclusion criteria |
The study population consists of postmenopausal women diagnosed with resectable breast cancer, who meet the following eligibility criteria: -Biopsy proven, ER positive invasive breast cancer (where ER positive is defined as equivalent to an ER “Quick or Allred score” of 3 or greater). -Tumour, measured on ultrasound, as greater than or equal to 2 cm in diameter. -Postmenopausal defined as: Any Age:- bilateral surgical oophorectomy amenorrhea 5 years (any cause)
Age 50 yrs:- natural amenorrhea for 1 year
Age <50 yrs: - if amenorrhea < 5 years or hysterectomy without bilateral surgical oophorectomy, then FSH, and/or LH and/or oestradiol must be assayed to confirm postmenospausal status
-Adequate haematological, renal and liver function, defined as a platelets of >100 x 109/l, white blood cell count of >3 x 109/l, creatinine <110 mmol/l, AST and/or ALT < 1.25 x upper limit of normal -Patients must be fit to complete surgery for their breast cancer -Written informed consent - ECOG performance status 0,1 or 2
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E.4 | Principal exclusion criteria |
-Bilateral breast cancer. -Evidence of distant metastases (M1). -Patients who have received previous treatment for invasive breast cancer. -Concomitant active malignancy. -Co-morbid disease which would preclude safe surgical treatment of the primary cancer. - Other physical or psychiatric disorder that may interfere with subject compliance, adequate informed consent or determine the causality of adverse events. - Contraindications to celecoxib: active peptic ulcer disease, renal impairment, asthma exacerbated by NSAIDS, congestive cardiac failure (NYHAII-IV*), ischaemic heart disease, cerebrovascular disease, uncontrolled hypertension. -Patients with an ongoing requirement for regular NSAID or COX2 inhibitor therapy (Asprin 75mg daily is permitted). -Regular selective COX 2 inhibitor use in the 2 years prior to randomisation -History of hypersensitivity to celecoxib, exemestane or letrozole or to any of the excipients (see section 6.1). -Known hypersensitivity to sulphonamides. -Patients who have experienced asthma, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria or other allergic-type reactions after taking acetylsalicylic acid or NSAIDs including COX-2 inhibitors. -Inflammatory bowel disease. -Patients with ongoing requirements for fluconazole or ketoconazole therapy. -Patients with ongoing requirement for lithium therapy. -Patients with ongoing requirement for ACE inhibitor therapy. -Patients who are on warfarin or heparin .
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint is objective clinical response (Complete Response, Partial Response) during neoadjuvant treatment.
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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 | 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) | Yes |
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 | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.1.7.1 | Other trial design description |
Randomised clinical trial with placebo controlled comparisons |
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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 | Yes |
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 | 80 |
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). For the purposes of Multicentre Research Ethics Committee approval, the study end date is deemed to be the date of last data capture. Recruitment period is estimated as 4 years to be followed by 5 years follow up.
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |