Study to Compare the Effects of AZD9496 vs Fulvestrant in Breast Cancer.

Phase 1

Completed

• Conditions: Postmenopausal Women With ER+ HER2- Primary Breast Cancer
• Interventions: Drug: Standard Arm - Fulvestrant; Drug: AZD9496

• Registration Number: NCT03236974
• Lead Sponsor: AstraZeneca

Brief Summary

This is an open label randomised multicentre pre-surgical pharmacodynamics study to compare and assess the biological effects of AZD9496 and fulvestrant in postmenopausal women with estrogen receptor (ER) positive (ER+), human epidermal growth factor receptor 2 (HER-2) negative (HER2-) primary breast cancer.

Patients will receive AZD9496 or fulvestrant and will have an on-treatment image

-guided core biopsy after 5-14 days of commencing treatment.

Detailed Description

This is an open label, randomized, multi-centre study in postmenopausal women with primary ER+ HER2- breast cancer. Patients will be randomised to an oral dose of 250 mg bd AZD9496 or 500mg fulvestrant i.m. administered on one occasion. Patients diagnosed with primary breast cancer who are scheduled for surgery with curative intent will be consented to the study including consent to use the formalin fixed paraffin embedded (FFPE) diagnostic tumor biopsy sample and fresh frozen tumor biopsy sample (if available) for research purposes. Patients may also consent to provide an optional pretreatment fresh frozen tumor biopsy sample if this was not obtained at the time of initial diagnostic biopsy. If the diagnostic biopsy was taken ≥ 6 weeks prior to starting treatment or was not of sufficient quality, new tumor core biopsies (FFPE and fresh frozen) must be taken. Following the screening visit, eligible patients will be randomised to receive one of the following study treatments:

* AZD9496 administered at 250 mg bd orally for 5-14 days commencing on Day 1, and continuing up to the day of biopsy OR

* fulvestrant 500 mg administered as two consecutive 5 ml intramuscular injections on Day 1, one in each buttock.

After the morning dose of AZD9496 on the day of biopsy dosing will be stopped. If following initiation of AZD9496 treatment, dosing will be stopped if biopsy is postponed beyond Day 14. Patients will be considered not evaluable for the study if biopsy is postponed beyond day 14 of AZD9496/fulvestrant treatment initiation. Core tumor biopsies will be taken at either the time of definitive surgery or at a separate visit prior to surgery in the period between (and including) day 5 and day 14. Subjects who are scheduled to start a subsequent neoadjuvant therapy must have their core tumor biopsies performed before commencing neoadjuvant treatment.

Study Timeline

• Study First Submitted: 2017-07-18
• Study First Submitted QC: 2017-08-01
• Study First Posted: 2017-08-02
• Study Start: 2017-10-05
• Primary Completion: 2019-02-12
• Study Completion: 2019-02-12
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-05
• Last Update Posted: 2020-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 49

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard arm	Standard Arm - Fulvestrant	Fulvestrant, 500 mg
AZD9496	AZD9496	250 mg bd taken orally for 5-14 days

Primary Outcome Measures

Name	Time	Method
Pharmacodynamics changes to estrogen receptor (ER) expression following treatment with AZD9496 or fulvestrant	Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment	Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. ER expression

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamics changes to progesterone receptor (PgR) expression following treatment with AZD9496 or fulvestrant	Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment	Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. PgR expression
Pharmacodynamics changes to Ki67 protein biomarker expression following treatment with AZD9496 or fulvestrant	Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment	Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. Ki67 protein biomarker expression
Safety and tolerability of AZD9496	From first dose until 28 days after last dose of AZD9496	Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data, vital signs and ECG changes.
Safety and tolerability of fulvestrant	From first dose until 28 days after fulvestrant	Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data and vital signs
Plasma concentration of AZD9496 - stand alone biopsy visit option	Blood samples collected close as possible to time of biopsy, 1-2 hours after biopsy and optional 3-4 hours after biopsy	Determination of AZD9496 concentrations in plasma
Plasma concentration of fulvestrant	A blood sample will be collected anytime before biopsy.	Determination of fulvestrant concentration in plasma
Plasma concentration of AZD9496 - on the table biopsy option	Blood samples collected close as possible to time of biopsy, at least 2 hours after biopsy and 8-12 hours after last dose or at discharge which is defined as up to 12 hours after last dose	Determination of AZD9496 concentration in plasma

Trial Locations

Locations (1)

Research Site; 🇬🇧 Sutton In Ashfield, United Kingdom