Safety and Efficacy of AZD4547 in Combination With Fulvestrant vs. Fulvestrant Alone in ER+ Breast Cancer Patients

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and effectiveness of AZD4547 in combination with fulvestrant vs. fulvestrant alone in ER+ breast cancer patients with FGFR1 polysomy (FISH4/5) or gene amplification (FISH 6)

Official Title
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A Randomised Double-blind Phase IIa Study (With Combination Safety Run-in) to Assess the Safety and Efficacy of AZD4547 in Combination With Fulvestrant vs. Fulvestrant Alone in ER+ Breast Cancer Patients With FGFR1 Polysomy or Gene Amplification Who Have Progressed Following Treatment With Prior Endocrine Therapy (Adjuvant or First-line Metastatic) (GLOW)

Conditions
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FGFR Inhibition, Pharmacokinetics, Biomarkers, ER+ Breast Cancer

Intervention / Treatment
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* Drug: AZD4547
* Drug: Exemestane
* Drug: Placebo
* Drug: Fulvestrant


Participation Criteria
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Eligibility Criteria
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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 AL Rand 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. Rand 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 Exclusion Criteria: Prior exposure to exemestane (safety run-in) / fulvestrant (randomized 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 (Randomized phase), including castor oil, or drugs with a similar chemical structure or class to AZD4547 or exemestane or fulvestrant. Randomized phase IIa: bleeding/blood clotting conditions that would prevent the administration of the fulvestrant injection into the buttocks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD4547 + exemestane<br>Safety run-in: AZD4547 plus exemestane | Drug: AZD4547<br>* Tablet oral twice daily<br>Drug: Exemestane<br>* Tablet oral once daily<br>|
| Experimental: AZD4547 + fulvestrant<br>A Randomised phase IIa: AZD4547 plus fulvestrant | Drug: AZD4547<br>* Tablet oral twice daily<br>Drug: Fulvestrant<br>* A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration<br>|
| Placebo Comparator: Placebo + fulvestrant<br>Randomised phase IIa: Matching placebo plus fulvestrant | Drug: Placebo<br>* Tablet oral twice daily<br>Drug: Fulvestrant<br>* A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability in Terms of Number of Patients With Adverse Events (Serious and Non-serious) |  | 3 years, 10 months (Adverse events recorded from patient screening to discontinuation plus 28 days safety follow-up). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ER+, Breast Cancer, FGFR1, Exemestane, AZD4547, Fulvestrant