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

NCT ID: NCT01202591

Last Updated: 2016-02-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-12-31

Study Completion Date

2014-10-31

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)

Detailed Description

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Conditions

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FGFR Inhibition, Pharmacokinetics, Biomarkers ER+ Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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AZD4547 + exemestane

Safety run-in: AZD4547 plus exemestane

Group Type EXPERIMENTAL

AZD4547

Intervention Type DRUG

Tablet oral twice daily

Exemestane

Intervention Type DRUG

Tablet oral once daily

AZD4547 + fulvestrant

A Randomised phase IIa: AZD4547 plus fulvestrant

Group Type EXPERIMENTAL

AZD4547

Intervention Type DRUG

Tablet oral twice daily

Fulvestrant

Intervention Type DRUG

A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration

Placebo + fulvestrant

Randomised phase IIa: Matching placebo plus fulvestrant

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Tablet oral twice daily

Fulvestrant

Intervention Type DRUG

A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration

Interventions

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AZD4547

Tablet oral twice daily

Intervention Type DRUG

Exemestane

Tablet oral once daily

Intervention Type DRUG

Placebo

Tablet oral twice daily

Intervention Type DRUG

Fulvestrant

A monthly intramuscular injection of a depot formulation with a loading dose 14 days after initial administration

Intervention Type DRUG

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Donal Landers

Role: STUDY_DIRECTOR

AstraZeneca

Locations

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Research Site

Leuven, , Belgium

Site Status

Research Site

Namur, , Belgium

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Research Site

Brno, , Czechia

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Prague, , Czechia

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Research Site

Villejuif, , France

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Research Site

Erlangen, , Germany

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München, , Germany

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Research Site

Rostock, , Germany

Site Status

Research Site

Budapest, , Hungary

Site Status

Research Site

Kaposvár, , Hungary

Site Status

Research Site

Nyíregyháza, , Hungary

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Szeged, , Hungary

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Genova, , Italy

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Research Site

Lido di Camaiore, , Italy

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Roma, , Italy

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Research Site

Cluj-Napoca, , Romania

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Dundee, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Oxford, , United Kingdom

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Research Site

Sutton, , United Kingdom

Site Status

Countries

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Belgium Czechia France Germany Hungary Italy Romania United Kingdom

Other Identifiers

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2010-021220-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D2610C00003

Identifier Type: -

Identifier Source: org_study_id

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