E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | 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 |
Safety run-in: To assess the safety and tolerability and to determine the dose of AZD4547 to be used in combination with a standard dose of exemestane, in the randomised phase IIa part of the study
Randomised phase IIa: To assess the relative efficacy of AZD4547 in combination with exemestane compared with exemestane + placebo by comparison of the change in tumour size at 12 weeks in all randomised patients and also in the FGFR1 amplified (FISH score 6) patients alone |
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E.2.2 | Secondary objectives of the trial |
Safety run-in: To investigate the pharmacokinetics (PK) of exemestane when given alone and in combination with AZD4547 and the PK of of AZD4547 when given in combination with exemestane
Randomised phase IIa: In all randomised patients and also in the FGFR1 amplified (FISH score 6) patients alone to assess the relative efficacy of AZD4547 in combination with exemestane compared with exemestane + placebo by assessment of 1)progression-free survival 2) objective response rate 3 )percentage of patients without progressive disease at 12 weeks 4) safety and tolerability and 5) PK of AZD4547 and exemestane when given in combination
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Both Safety Run In and Phase II portion: 1. Post-menopausal women (either through bilateral oophorectomy or amenorrhoeic for 24 months) 2. Histological confirmation of breast cancer, with documented positive oestrogen receptor status (ER+) 3. Fulfils specific criteria for previous treatment of breast cancer: a. Relapsing during, or within 12 months of completion of, a single regimen of adjuvant endocrine therapy (either non-steroidal AI or tamoxifen or a combination of both) or b. Progression following first line endocrine therapy with a non-steroidal AI and/or tamoxifen for advanced breast cancer. Co-administration of a targeted agent with the non-steroidal AI is permitted providing all toxicities have recovered to CTCAE Grade 1 or below. One regimen of adjuvant endocrine therapy prior to the advanced breast cancer therapy is permitted
Randomised phase IIa portion only: 1. Mandatory provision of tumour biopsy for AZ approved laboratory confirmation of FGFR1 polysomy or gene amplification 2. At least one measurable lesion |
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E.4 | Principal exclusion criteria |
1. More than one regimen of endocrine therapy for advanced breast cancer 2. Previous exposure to exemestane or any agent known to inhibit FGFRs 3. Any prior chemotherapy for advanced breast cancer 4. Abnormal cardiac function 5. Any evidence of severe or uncontrolled systemic diseases 6. Inadequate bone marrow reserve or organ function 7. Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring steroids for at least 4 weeks prior to start of study treatment |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and Tolerability AZD4547 / exemestane pharmacokinetics Investigator assessment of patient disease status (safety run-in) Tumour response as assessed by RECIST 1.1 (PIIa)
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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 | Yes |
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 | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 defined as the last visit of the last patient undergoing the study. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |