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

AstraZeneca

Status and phase: Completed; Phase 2; Phase 1

Conditions: ER+ Breast Cancer; FGFR Inhibition, Pharmacokinetics, Biomarkers

Treatments: Drug: AZD4547; Drug: Placebo; Drug: Exemestane; Drug: Fulvestrant

Study type: Interventional

Funder types: Industry

Identifiers

NCT01202591

2010-021220-10 (EudraCT Number)

D2610C00003

Details and patient eligibility

About

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)

Enrollment: 127 patients

Sex: Female

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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127 participants in 3 patient groups, including a placebo group

AZD4547 + exemestane

Experimental group

Description:

Safety run-in: AZD4547 plus exemestane

Treatment:

Drug: Exemestane

Drug: AZD4547

AZD4547 + fulvestrant

Experimental group

Description:

A Randomised phase IIa: AZD4547 plus fulvestrant

Treatment:

Drug: Fulvestrant

Drug: AZD4547

Placebo + fulvestrant

Placebo Comparator group

Description:

Randomised phase IIa: Matching placebo plus fulvestrant

Treatment:

Drug: Fulvestrant

Drug: Placebo