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

ER+ Breast Cancer Clinical Trial

— GLOW  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01202591
• Other study ID #: D2610C00003
• Secondary ID: 2010-021220-10
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 14, 2010
• Last updated: January 13, 2016
• Start date: December 2010
• Est. completion date: October 2014

Study information

• Verified date: January 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Direction Générale de la SantéFrance: French Data Protection AuthorityFrance: Haute Autorité de Santé Transparency CommissionFrance: Institutional Ethical CommitteeFrance: Ministry of HealthFrance: National Consultative Ethics Committee for Health and Life SciencesGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyItaly: National Institute of HealthNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Romania: National Medicines AgencyRussia: Ministry of Health of the Russian FederationUnited Kingdom: Department of HealthUnited Kingdom: Food Standards AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health ServiceUnited Kingdom: Research Ethics Committee
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: October 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 99 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• ER+ Breast Cancer
• FGFR Inhibition, Pharmacokinetics, Biomarkers

Intervention

Drug:
• AZD4547
Tablet oral twice daily
• Exemestane
Tablet oral once daily
• Placebo
Tablet oral twice daily
• Fulvestrant
A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration

Locations

Country	Name	City	State
Belgium	Research Site	Leuven
Belgium	Research Site	Namur
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Praha 4
France	Research Site	Villejuif Cedex
Germany	Research Site	Erlangen
Germany	Research Site	München
Germany	Research Site	Rostock
Hungary	Research Site	Budapest
Hungary	Research Site	Kaposvár
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Szeged
Italy	Research Site	Genova
Italy	Research Site	Lido di Camaiore
Italy	Research Site	Roma
Romania	Research Site	Cluj Napoca
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Oxford
United Kingdom	Research Site	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Belgium,  Czech Republic,  France,  Germany,  Hungary,  Italy,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Yes