ER+ Breast cancer MedDRA version: 15.1 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: AZD4547 20mg white tablets
Product Code: AZD4547
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: not available
CAS Number: 1035270-39-3
Current Sponsor code: AZD4547
Other d
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Post-menopausal women (either through bilateral oophorectomy or amenorrhoeic for 24 months) Histological confirmation of Breast Cancer with documented ER+ receptor status Safety run-in: Relapsing during/within 12 months of completion of a single regimen of adjuvant endocrine therapy with non-steroidal AI and/ tamoxifen or progression following 1st line endocrine therapy with non-steroidal AI Randomised phase IIa: Received at least 1 prior endocrine therapy in the metastatic setting or have relapsed during/ within 6 months of completion of adjuvant endocrine therapy (either non-steroidal AI or tamoxifen or a combination of both). Chemotherapy administered in the adjuvant setting is permitted. Randomised phase IIa: Mandatory provision of tumour sample to confirm FGFR1 polysomy or gene amplification At least one measurable lesion that can be accurately assessed by CT/MRI/x-ray at baseline and follow up visits Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Prior exposure to exemestane (safety run-in) / fulvestrant (randomised phase IIa), or any agent known to inhibit FGFRs. More than 1 prior regimen of chemotherapy for breast cancer ECG recordings that demonstrate significant abnormalities in cardiac rate, rhythm or conduction History of hypersensitivity to active or inactive excipients of AZD4547 or exemestane (safety run-in ) or fulvestrant (Randomised phase), including castor oil, or drugs with a similar chemical structure or class to AZD4547 or exemestane or fulvestrant. Randomised phase IIa: bleeding/blood clotting conditions that would prevent the administration of the fulvestrant injection into the buttocks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Safety run-in: To investigate the pharmacokinetics of AZD4547 and exemestane, when given in combination Randomised phase IIa with embedded safety assessment: To assess the relative efficacy of AZD4547 in combination with fulvestrant compared with fulvestrant + placebo by comparison of the change in tumour size at 12 weeks, objective response rate, duration of response in all randomised patients, patients with tumours that have FGFR1 gene amplification (FISH 6), and patients with moderate to high FGFR1 gene amplification alone ;Primary end point(s): Safety Run-in: Safety and tolerability in terms of number of patients with Adverse events (serious and non-serious) Randomised phase IIa: To assess the relative tumour response of AZD4547 in combination with fulvestrant compared with fulvestrant + placebo by measuring Progression Free Survival via measurement of Response Evaluation Criteria in Solid Tumours (RECIST);Timepoint(s) of evaluation of this end point: Adverse events recorded from patient screening to discontinuation from study plus 28 days safety follow-up RECIST assessments at Baseline, week 12 and then every 8 weeks until objective disease progression;Main Objective: Safety Run In: To assess the safety and tolerability and to determine a dose of AZD4547 in combination with a standard dose of exemestane. Randomised Phase IIa with embedded safety assessment: To assess the relative efficacy and safety of AZD4547 in Combination with fulvestrant vs. fulvestrant alone by progression free survival. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Run-in: To investigate the Pharmacokinetics(PK)/Pharmacodynamics(PD) of AZD4547 and exemestane when given in combination by measuring blood plasma concerntrations Measure the effects of AZD4547 on circulating oestradiol. Randomised phase IIa: Measurement in the change of tumour size at week 12 across the two arms as measured by RECIST. Measurement of Objective Response Rate (ORR) (the percentage of patients with at least one visit response). As measured by RECIST. Duration of Response (DoR) the time taken from first response until progression or death. As measured by RECIST Measurement of the percentage of patients without progressive disease at 12 weeks. Measurement of the laboratory changes in clinical chemistry, haematology and urine as compared to baseline Measurement of changes in vital signs compared to baseline. Measurement of Health Related Quality of Life using a Cancer Quality of Life Questionnaire.;Timepoint(s) of evaluation of this end point: Blood sample taken on last day of exemestane monotherapy and Cycle 1 day 7 (AZD4547+exemestane), (sampling time: pre-dose to 10-12h) Blood sample for oestradiol level taken at screening, on last day of exemestane monotherapy and day 7 of cycle 1 RECIST assessment at baseline and week 12. RECIST assessmentat baseline, week 12 and then every 8 weeks until objective disease progression RECIST assessment at baseline, week 12 and then every 8 weeks until progression RECIST assessment at Baseline and week 12 Laboratory data will be collected from screening to 28 days post drug discontinuation Vital signs will be recorded from screening to 28 days after study drug discontinuation Questionaire collected at screening and at each visit up to 28 days post discontinuation of study drug. | — |
Countries
Belgium, Czech Republic, France, Germany, Hungary, Italy, Romania, Russian Federation, United Kingdom
Outcome results
None listed