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

Phase 1

Completed

• Conditions: FGFR Inhibition, Pharmacokinetics, Biomarkers; ER+ Breast Cancer
• Interventions: Drug: AZD4547; Drug: Placebo; Drug: Exemestane; Drug: Fulvestrant

• Registration Number: NCT01202591
• Lead Sponsor: AstraZeneca

Brief Summary

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-09-14
• Study First Submitted QC: 2010-09-14
• Study First Posted: 2010-09-16
• Study Start: 2010-12
• Primary Completion: 2014-09
• Study Completion: 2014-10
• Results First Submitted: 2015-09-07
• Status Verified: 2016-01
• Results First Submitted QC: 2016-01-13
• Last Update Submitted: 2016-01-13
• Results First Posted: 2016-02-11
• Last Update Posted: 2016-02-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 127

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AZD4547 + fulvestrant	AZD4547	A Randomised phase IIa: AZD4547 plus fulvestrant
AZD4547 + exemestane	AZD4547	Safety run-in: AZD4547 plus exemestane
AZD4547 + exemestane	Exemestane	Safety run-in: AZD4547 plus exemestane
Placebo + fulvestrant	Placebo	Randomised phase IIa: Matching placebo plus fulvestrant
AZD4547 + fulvestrant	Fulvestrant	A Randomised phase IIa: AZD4547 plus fulvestrant
Placebo + fulvestrant	Fulvestrant	Randomised phase IIa: Matching placebo plus fulvestrant

Primary Outcome Measures

Name	Time	Method
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).

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sutton, United Kingdom