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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01202591
First received: September 14, 2010
Last updated: June 25, 2014
Last verified: June 2014
  Purpose

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)


Condition Intervention Phase
FGFR Inhibition, Pharmacokinetics, Biomarkers
ER+ Breast Cancer
Drug: AZD4547
Drug: Exemestane
Drug: Placebo
Drug: Fulvestrant
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Safety Run-in: Safety and tolerability in terms of number of patients with Adverse events (serious and non-serious) [ Time Frame: Adverse events recorded from patient screening to discontinuation from study plus 28 days safety follow-up ] [ Designated as safety issue: Yes ]
  • 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) [ Time Frame: RECIST assessments at Baseline, week 12 and then every 8 weeks until objective disease progression ] [ Designated as safety issue: No ]
    PFS- Progression Free Survival


Secondary Outcome Measures:
  • Safety Run-in: To investigate the Pharmacokinetics(PK)/Pharmacodynamics(PD) of AZD4547 and exemestane when given in combination by measuring blood plasma concentrations [ Time Frame: Blood sample taken on last day of exemestane monotherapy and Cycle 1 day 7 (AZD4547+exemestane), (sampling time: pre-dose to 10-12h) ] [ Designated as safety issue: No ]
  • Safety Run-in: Measure the effects of AZD4547 on circulating oestradiol [ Time Frame: Blood sample for oestradiol level taken at screening, on last day of exemestane monotherapy and day 7 of cycle 1 ] [ Designated as safety issue: No ]
  • Randomized phase IIa: Measurement in the change of tumor size at week 12 across the two arms as measured by RECIST. [ Time Frame: RECIST assessment at baseline and week 12. ] [ Designated as safety issue: No ]
  • Randomized phase IIa: Measurement of Objective Response Rate (ORR) (the percentage of patients with at least one visit response). As measured by RECIST. [ Time Frame: RECIST assessment at baseline, week 12 and then every 8 weeks until objective disease progression ] [ Designated as safety issue: No ]
  • Randomized phase IIa: Duration of Response (DoR) the time taken from first response until progression or death. As measured by RECIST. [ Time Frame: RECIST assessment at baseline, week 12 and then every 8 weeks until progression. ] [ Designated as safety issue: No ]
  • Randomized phase IIa: Measurement of the percentage of patients without progressive disease at 12 weeks. [ Time Frame: RECIST assessment at Baseline and week 12 ] [ Designated as safety issue: No ]
  • Randomized phase IIa: Measurement of the laboratory changes in clinical chemistry, haematology and urine as compared to baseline [ Time Frame: Laboratory data will be collected from screening to 28 days post drug discontinuation. ] [ Designated as safety issue: Yes ]
  • Randomized phase IIa: Measurement of changes in vital signs compared to baseline. [ Time Frame: Vital signs will be recorded from screening to 28 days after study drug discontinuation ] [ Designated as safety issue: Yes ]
  • Randomized phase IIa: Measurement of Health Related Quality of Life using a Cancer Quality of Life Questionnaire. [ Time Frame: Questionaire collected at screening and at each visit up to 28 days post discontinuation of study drug. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 900
Study Start Date: December 2010
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZD4547 + exemestane
Safety run-in: AZD4547 plus exemestane
Drug: AZD4547
Tablet oral twice daily
Drug: Exemestane
Tablet oral once daily
Experimental: AZD4547 + fulvestrant
A Randomised phase IIa: AZD4547 plus fulvestrant
Drug: AZD4547
Tablet oral twice daily
Drug: Fulvestrant
A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration
Placebo Comparator: Placebo + fulvestrant
Randomised phase IIa: Matching placebo plus fulvestrant
Drug: Placebo
Tablet oral twice daily
Drug: Fulvestrant
A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01202591

Locations
Belgium
Research Site
Leuven, Belgium
Research Site
Namur, Belgium
Czech Republic
Research Site
Brno, Czech Republic
Research Site
Praha 4, Czech Republic
France
Research Site
Pierre Benite Cedex, France
Research Site
Villejuif Cedex, France
Germany
Research Site
Erlangen, Germany
Research Site
München, Germany
Research Site
Rostock, Germany
Hungary
Research Site
Budapest, Hungary
Research Site
Kaposvár, Hungary
Research Site
Nyíregyháza, Hungary
Research Site
Szeged, Hungary
Italy
Research Site
Genova, Italy
Research Site
Lido di Camaiore, Italy
Research Site
Roma, Italy
Romania
Research Site
Cluj Napoca, Romania
Russian Federation
Research Site
Kuzmolovsky, Russian Federation
Research Site
Moscow, Russian Federation
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, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Paul Stockman AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01202591     History of Changes
Other Study ID Numbers: D2610C00003, 2010-021220-10
Study First Received: September 14, 2010
Last Updated: June 25, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Direction Générale de la Santé
France: French Data Protection Authority
France: Haute Autorité de Santé Transparency Commission
France: Institutional Ethical Committee
France: Ministry of Health
France: National Consultative Ethics Committee for Health and Life Sciences
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: National Institute of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
United Kingdom: Department of Health
United Kingdom: Food Standards Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: Research Ethics Committee

Keywords provided by AstraZeneca:
Breast Cancer
ER+
FGFR1
Exemestane
AZD4547
Fulvestrant

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Exemestane
Fulvestrant
Estradiol
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogens
Hormones

ClinicalTrials.gov processed this record on October 19, 2014