E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic ER+/PgR+/erbB2-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 | Information not present in EudraCT |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy, in terms of PFS assessed by an independent radiology vendor, of bosutinib in combination with letrozole versus letrozole alone as first line treatment or as recurrence of adjuvant treatment for ER+/PgR+/erbB2- advanced or MBC in postmenopausal women. |
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E.2.2 | Secondary objectives of the trial |
· To evaluate the safety profile of bosutinib in combination with letrozole.
· To evaluate the PK of both bosutinib and letrozole in combination.
· To evaluate additional efficacy parameters such as ORR, overall survival (OS) at 3 years, duration of response, and PFS assessed by investigational sites.
· To examine the health-related quality of life (HRQoL) of bosutinib in combination with letrozole versus letrozole alone.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Surgically sterile or postmenopausal women.
· Confirmed pathologic diagnosis of breast cancer.
· Locally advanced, metastatic, or locoregional recurrent breast cancer 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.
· At least 1 radiologically measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).
· Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. |
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E.4 | Principal exclusion criteria |
· Prior letrozole (except in adjuvant setting), prior bosutinib, or any other prior anti-Src therapy.
· Prior endocrine treatment for locally advanced or MBC.
· More than 1 prior cytotoxic chemotherapy regimen in metastatic setting. (Subjects may have received prior adjuvant or neoadjuvant chemotherapy.)
· Adjuvant AI therapy ≤12 months before day 1 of treatment.
· Adjuvant tamoxifen therapy ≤2 weeks before day 1 of treatment.
· Bone or skin as the only site of disease.
· Major surgery or radiotherapy within 14 days of treatment day 1.
· Extensive visceral disease or active central nervous system (CNS) disease.
· Any other cancer within 5 years of screening with the exception of ER+ contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.
· 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) |
Progression-Free Survival PFS is the time interval from the date of randomization until the first date on which recurrence or progression, or death due to any cause, is documented, censored at the last tumor evaluation.
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
proteomyc and transcriptomic |
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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 | 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) | 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.8.6 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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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 | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |