E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic ER+/PgR+/Her2-breast cancer in post-menopausal women |
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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 | 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 |
The primary objective is to compare efficacy, as measured by PFS and assessed by an independent radiology read, of bosutinib in combination with exemestane with that of exemestane alone. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the safety profile of bosutinib in combination with exemestane, to evaluate the population pharmacokinetics (PK) of bosutinib in combination with exemestane, and to evaluate additional efficacy parameters: PFS per sites assessment, overall response rate, 2-year overall survival, and duration of response.
An exploratory objective is to analyze biomarkers for prediction of response to treatment with bosutinib in combination with exemestane |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Post-menopausal women. • Confirmed pathologic diagnosis of breast cancer. • Locally advanced or metastatic, or loco-regional recurrent and not amenable to curative treatment with surgery or radiotherapy. • Documented ER+ and/or PgR+ and erbB2- tumor based on most recently analyzed biopsy, as documented by a local laboratory. • Progression of locally advanced or metastatic disease during treatment with a non-steroidal AI or tamoxifen, or progression during treatment with (or within 6 months of discontinuation of) an adjuvant non-steroidal AI. • At least 1 radiologically measurable lesion as defined by RECIST • ECOG performance status 0-2. |
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E.4 | Principal exclusion criteria |
• Prior exemestane, prior bosutinib, or any other prior Src inhibitor. • More than 1 prior endocrine treatment for locally advanced or metastatic breast cancer. • More than 1 prior chemotherapy regimen in metastatic setting • Subjects with bone or skin as the only site of disease • Extensive visceral disease or active CNS disease. • Any other cancer within 5 years of screening with the exception of adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin. • Major surgery or radiotherapy within 14 days of treatment day 1. • No adequate hepatic/renal/bone marrow function. • History of clinically significant or uncontrolled cardiac disease • Serious concurrent illness. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the efficacy, in terms of progression free survival (PFS) assessed by an independent radiology vendor, of bosutinib in combination with exemestane versus exemestane alone as second line treatment for ER+/PgR+/HER2- advanced or metastatic breast cancer in postmenopausal women |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | 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 | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
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 end of the study is when the last subject has completed 24 months follow-up for survival or when the last subject has expired, whatever occurs first. |
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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 | 3 |
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 |