E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic breast cancer, resistant to aromatase inhibitors |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic 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 |
Main objective : To compare the clinical benefit rate between fulvestrant plus enzastaurin and fulvestrant plus placebo in Aromatase Inhibitor resistant MBC. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives: • to compare the clinical benefit rate between 2 pairs of patient cohorts: (1) fulvestrant plus enzastaurin BID and fulvestrant plus placebo; (2) fulvestrant plus enzastaurin QD and fulvestrant plus placebo • to compare the following endpoints between 3 pairs of patient cohorts: (1) all fulvestrant plus enzastaurin patients (BID+QD) and fulvestrant plus placebo; (2) fulvestrant plus enzastaurin BID and fulvestrant plus placebo; (3) fulvestrant plus enzastaurin QD and fulvestrant plus placebo: response rates (RR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines duration of clinical benefit progression-free survival (PFS) safety and adverse event profile in both treatment arms using Common Terminology Criteria for Adverse Events . • to assess biomarkers relevant to enzastaurin and the disease state, as well as their correlation to clinical outcome.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Female patients with a histological-documented diagnosis of locally advanced or metastatic breast cancer. The primary or metastatic tumor must be ER and/or PtR receptor positive. Note: Hormone receptor positivity is defined as ER or PtR >10 fmol/mg by biochemical assay or 10% positive cells by immunohistochemistry [2] Patients are resistant to AI therapy • AI was administered in the adjuvant setting: patient should have been on treatment for at least 1 year and have had an objective recurrence during this treatment or in the first year after finishing it • AI was administered in advanced disease: If patients have not received previous chemotherapy for MBC, they must have achieved a tumor response or stabilization lasting at least 6 months and have had an objective progression during treatment If patients have received previous chemotherapy for MBC, they can have 3 different situations : • Chemotherapy → AI (as maintenance of response). They must have received the AI lasting at least 6 months and have had an objective progression during treatment • Chemotherapy → AI (at progression). They must have achieved a tumor response or stabilization lasting at least 6 months and have had an objective progression during treatment • AI → Chemotherapy. They must have achieved a tumor response or stabilization to the AI and have had an objective progression after chemotherapy.
[5] Measurable or nonmeasurable disease defined by: • At least 1 unidimensionally measurable lesion meeting RECIST (Protocol Attachment S023.5; Therasse et al. 2000) Guidelines. Positron emission tomography (PET) scans and ultrasounds may not be used • At least 1 nonmeasurable lesion whose presence is assessable using standard techniques or a spiral CT scan even though the lesion is smaller than the minimum size required for measurability (PET scans and ultrasounds may not be used). Patients with bone lesion(s) in the absence of measurable disease can be recruited provided they can be evaluated by X-ray, CT or MRI (patients with lesions assessed only by bone scan cannot be included)
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E.4 | Principal exclusion criteria |
[13] Have received treatment with more than 1 line of hormonal therapy in the metastatic setting [14] Have had prior treatment with fulvestrant, or enzastaurin [30] Patients with osteoporosis, defined as bone mineral density (BMD) T score <2.5 SD (standard deviation) or receiving treatment for osteoporosis. Note: Patients with BMD T score between 1 to 2.5 are defined as osteopenia, which, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient’s ability to complete the study
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measure is the clinical benefit rate. Clinical benefit (CB) is defined as the best response of CR, PR, and SD for 24 weeks duration. The CB rate is defined, for each treatment arm, as the number of patients with the best response of CR, PR, and SD for 24 weeks duration divided by the number of randomized and treated patients. |
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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 | 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 | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
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 | 3 |