E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced or recurrent endometrial cancer |
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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 | 10014733 |
E.1.2 | Term | Endometrial 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 determine the antitumour efficacy of BN83495 compared to megestrol acetate measured by progression free survival (PFS) in women with advanced and recurrent endometrial cancer.
PFS is defined as the time from randomisation until objecctive tumour progression or death from any cause.
Response and progression will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumours (RECIST) committee version 1.0. |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety and tolerability of BN83495 versus MA in this patient population. - To assess the following parameters of antitumour efficacy: - Clinical Benefit (CB): Complete Response (CR) + Partial Response (PR) + Stable Disease (SD) ≥12 weeks. - Overall Response (OR): CR + PR. - Time to Progression (TTP). - Duration of Response (DR) in responders. - Overall Survival (OS) at 1 and 2 years. - To assess quality of life (QoL) in this study using EuroQoL EQ-5D - To assess the effect of treatment on age-related frailty using an oncogeriatric assessment in patients > 65 years of age. - To explore the pharmacodynamic effects of BN83495 on plasma steriod hormone levels in post-menopausal women. - To determine the pharmacokinetic profile of BN83495 in this patient population after repeated daily administration by means of a population pharmacokinetic (PK) analysis.
In addition there are a number of exploratory objectives specified in the protocol. |
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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 |
Pharmacogenetic and Pharmacogenomic Testing:
Title, version and date: the same as main study X-55-58064-004
An assessment of genetic polymorphisms in genes which may be involved in BN83495 drug disposition and/or pharmacological effect will be undertaken using baseline blood sample. Pharmacogenomic testing will also be undertaken to identify biomarkers potentially predictive of response using microarrays, and to evaluate STS gene expression. |
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E.3 | Principal inclusion criteria |
1. Provision of written informed consent prior to any study related procedures. 2. Post-menopausal or ovariectomised female patients over the age of 18 years with advanced or recurrent endometrial cancer. 3. Histologically confirmed diagnosis of endometrial carcinoma. 4. Not eligible for surgery or radiotherapy. 5. Document ER and/or PR positivity in the primary tumour. ER positive is defined by at least 10% positive cells where the information is available. 6. No other history of malignant disease except treated basal cell or in situ cervical carcinoma. 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤2. 8. At least one measurable disease site (RECIST criteria version 1.0) - minimum indicator lesion size: 20mm (conventional techniques) or 10mm (spiral CT scan) - target lesions not situated in irradiated area 9. Life expectancy ≥6 months. 10. Adequate organ function as defined by the following criteria: - Haemogolobin ≥10g/dL - Absolute neutrophil count (ANC) ≥1500/µL - Platelets ≥100,000/µl 11. Patients must have recovered from surgery, radiotherapy and toxicities of adjuvant chemotherapy treatment if applicable. |
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E.4 | Principal exclusion criteria |
1. Use of any investigational agent in the 4 weeks prior to enrolment in this study 2. Prior systemic treatment for endometrial cancer (including hormonal treatment, chemotherapy, antiangiogenic or targeted therapies) with the exception of chemotherapy in the adjuvant setting having been completed at least 1 year prior to randomisation. 3. Known central nervous system (CNS) metastases 4. Ongoing cardiac dysrhythmias of NCI CTC adverse event (AE) grade ≥2, atrial fibrillation of any grade, QTcF interval >460 msec 5. Patients with contraindications to MA including hypersensitivity to one of the components of the drug product, any significant arterial or venous thromboembolic event and/or uncontrolled hypertension 6. Concomitant use of systemic carbonic anhydrase II inhibitors (e.g. acetazolamide, dichlorphenamide, methazolamide) 7. History of hypersensitivity to BN83495 or drugs with a similar chemical structure. 8. Likely to require treatment during the study with drugs that are not permitted by the study protocol (see Section 9.6). 9. Abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the patient's safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is PFS, defined as the time from randomisation until objective tumour progression or death [CPMP/EWP/205/95/Rev 3/ Corr 2 Guideline of the evaluation of anticancer medicinal products in man of Dec 05., FDA, Guidance for Industry, May 2007]. Response and progression will be evaluated using the international criteria proposed by the RECIST committee (version 1.0). Tumour response will be evaluated every 8 weeks. All responses will be confirmed ≥4 weeks after initially evidenced. Blinded central review of responses will be performed. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tumour Assessment via CT scan/MRI |
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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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 | No |
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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The study will be considered to have finished at the end of study visit of the last patient. The end of study visit will occur at the end of the post treatment follow up period, therefore the end of study visit will occur 28 days after the last treatment. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |