Clinical trial NCT01202591: Safety and Efficacy of AZD4547 in Combination With Fulvestrant vs. Fulvestrant Alone in ER+ Breast Cancer Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: FGFR Inhibition, Pharmacokinetics, Biomarkers
ER+ Breast Cancer
Keywords: Breast Cancer
ER+
FGFR1
Exemestane
AZD4547
Fulvestrant
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-09-16
Enrollment: 127
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility 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 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

Primary outcomes:
measure: Safety and Tolerability in Terms of Number of Patients With Adverse Events (Serious and Non-serious)
timeFrame: 3 years, 10 months (Adverse events recorded from patient screening to discontinuation plus 28 days safety follow-up).
Secondary outcomes:
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Research Site
city: Namur
country: Belgium
facility: Research Site
city: Brno
country: Czech Republic
facility: Research Site
city: Praha 4
country: Czech Republic
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Kaposvár
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Lido di Camaiore
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
city: Sutton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Donal Landers
role: STUDY_DIRECTOR
References: