E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced, Oestrogen Receptor Positive Breast Cancer for whom Prior Endocrine Therapies have Failed, One of which was an Aromatase Inhibitor |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057654 |
|
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 |
Primary Objective: The primary objective is to determine with a specified level of precision the clinical benefit rate (CBR) of up to 6 months treatment with trilostane 720 mg and concomitant hydrocortisone 20 mg in post menopausal women with advanced, ER positive breast cancer for whom prior endocrine therapies have failed, one of which was an AI.
|
|
E.2.2 | Secondary objectives of the trial |
Secondary Objectives: • To determine objective tumour response • To determine toxicity • To determine time to PD • To determine duration of response • To determine performance status
|
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
• Patients must provide written informed consent prior to any study procedures being performed and according to local ethics committee guidelines • Female patients aged over 18 years • Patients must be post-menopausal, defined as >12 months since last menses. In patients whose last menses was ≤12 months before start of treatment, follicle stimulating hormone (FSH) and luteinising hormone (LH) levels must be in post-menopausal range: FSH ≥35 IU/L and LH >40 IU/L • Patients must have histological diagnosis of ER positive breast cancer and have relapsed or are refractory to hormone therapies, one of which must have been a new generation AI (letrozole, exemestane or anastrozole), prior to Screening • Patients must have performance status ≤2 ECOG scale • Patients must be suitable for hormone therapy in the investigator’s opinion • Patients with a life expectancy of >3 months • Patients with bone metastases are eligible provided that they have evaluable sites of metastases that can be followed by x-ray, MRI/CT scan • Patients must have measurable disease according to the RECIST criteria • All prior hormonal therapy must have failed (ie, either relapsed or refractory) • Patients must have haemoglobin ≥9.0 g/dL (after transfusion if needed) at Screening • Patients must have a white blood cell (WBC) count ≥3,500/mm3 at Screening • Patients must have neutrophils ≥1,500/mm3 at Screening • Patients must have platelets ≥100,000/mm3 at Screening • Patients must have creatinine ≤1.5 x upper limit of normal (ULN) for the testing laboratory, or a creatinine clearance ≥60 mL/minute at Screening • Patients must have serum bilirubin ≤1.5 mg/dL at Screening • Patients must have aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) ≤2 x ULN, or if liver metastases by ultrasound or magnetic resonance imaging (MRI) scan ≤5 x ULN at Screening
|
|
E.4 | Principal exclusion criteria |
1) Patients with inflammatory breast cancer 2) Patients with concurrent medical or psychiatric problems, unrelated to breast cancer, which would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy 3) Patients who are hypocortisolaemic 4) Patients who have received treatment with another investigational therapy including hormonal therapy within 30 days or five half-lives (whichever is longer) prior to entry into the study 5) Patients who are presently receiving or expect to require concurrent chemotherapy, immunotherapy, radiotherapy or chronic corticosteroid therapy. Patients who have received prior adjuvant chemotherapy will be eligible, provided the chemotherapy was administered prior to hormonal therapy and its use was stopped at least 6 months prior to study enrolment 6) Any condition which, in the opinion of the investigator, makes the patient unsuitable for entry into the study 7) Patients with brain metastases 8) Patients with severe concurrent illness 9) Patients who previously participated in the study 10) Patients with known adrenal insufficiency
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
CBR is defined as the proportion of patients with any of the following assessments using the Response Evaluation Criteria in Solid Tumours (RECIST) system (see Appendix II) at both the 3-month and 6 month visits: • CR • PR • SD
CR and PR must be subsequently confirmed 4 weeks later.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
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) | 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 | No |
E.8.1.1 | Randomised | No |
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) | No |
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 | No |
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 | 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
| |
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 | |
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 |