Phase 1 Completed N=99 Basic Science

AZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer

Advanced Metastatic Breast Cancer

Source: ClinicalTrials.gov NCT01597388 ↗

Enrolled (actual)

Serious AEs

16.2%

Results posted

Oct 2018

Primary outcomePrimary: Adverse Events — 6; 13; 14; 10 Participants

Summary

The purpose of this study is to assess safety and tolerability of AZD2014 when given in combination with Fulvestrant

Outcome Measures

Outcome	Result	p-value
PRIMARY Adverse Events	6; 13; 14; 10; 37; 4	—
PRIMARY Adverse Events Leading to Dose Reduction of AZD2014	1; 7; 4; 6; 12; 0	—
PRIMARY Clinically Important Changes in Haematology Parameters	0; 0; 0; 0; 0; 0	—
PRIMARY Clinically Important Changes in Clinical Chemistry Parameters	0; 1; 3; 3; 0; 1	—
PRIMARY Left Ventricular Ejection Fraction	59.2; 64.0; 60.9; 61.4; 62.6; 62.5	—
PRIMARY QTcF Over 24 Hours	423.12; 421.92; 412.78; 415.95; 419.95; 427.13	—
PRIMARY Post-Baseline Glucose Elevation	3; 6; 7; 5; 29; 3	—
PRIMARY Sitting Diastolic Blood Pressure	72.8; 75.4; 77.4; 74.9; 74.4; 73.8	—
PRIMARY Sitting Systolic Blood Pressure	114.2; 126.3; 127.4; 125.2; 124.4; 122.3	—
PRIMARY Respiratory Rate	18.3; 17.5; 18.3; 17.8; 17.5; 17.5	—
PRIMARY Heart Rate	87.5; 84.5; 82.7; 81.0; 83.5; 73.5	—
PRIMARY Body Temperature	36.35; 36.44; 36.46; 36.48; 36.57; 36.60	—
PRIMARY Oxygen Saturation	97.0; 97.2; 96.8; 96.7; 97.8; 97.0	—
PRIMARY AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	971.2; 1023; 1895; 2166	—
PRIMARY AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	3478; 5080; 9723; 12590	—
PRIMARY AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	3697; 6006; 11650; 15790	—
PRIMARY AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	3458; 5832; 11500; 15660	—
PRIMARY AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	3731; 6392; 12360; 17360	—
PRIMARY AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	3165; 1933; 4238; 2454	—
PRIMARY Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	1.1; 2.0; 1.5; 3.0	—
PRIMARY AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant	19810; 13760; 26570; 16150	—
PRIMARY AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	1374; 1785; 2409; 2327	—
PRIMARY Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	1.3; 1.0; 1.5; 1.5	—
PRIMARY AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant	8611; 11810; 13510; 15580	—
SECONDARY AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.	889.4; 968.5; 1678; 1942	—
SECONDARY Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.	1.00; 1.00; 1.10; 1.80	—
SECONDARY Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.	3233; 4666; 8185; 11470	—
SECONDARY Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.	3494; 5543; 9843; 15110	—
SECONDARY Objective Response Rate	0; 2; 2; 1; 2; 1	—
SECONDARY Best Objective Response (BOR)	0; 0; 0; 0; 0; 0	—
SECONDARY Duration of Response (DoR)	5.1; 9.7; NA; NA; NA; NA	—
SECONDARY Clinical Benefit Rate (CBR) at 24 Weeks	2; 6; 4; 7; 11; 2	—
SECONDARY Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.	NA; -9.37; -5.83; NA; -0.46; -3.57	—
SECONDARY Progression Free Survival	49.4; 35.6; 17.3; 78.3; 22.6; 33.9	—
SECONDARY Progression Free Survival at 26 Weeks	33; 38; 21; 60; 35; 50	—

Eligibility Criteria

Inclusion Criteria

Provision of signed and dated written informed consent prior to any study specific procedures, sampling analysis
Aged at least 18
At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray and is suitable for repeated assessment
Histological or cytological confirmation of an ER+ advanced metastatic breast cancer tumour that is eligible for treatment with fulvestrant
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Patients must have evidence of non-child-bearing potential.

Exclusion Criteria

Prior chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents, and any investigational agents within 14 days of starting study treatment (not including palliative radiotherapy at focal sites)
Major surgery within 4 weeks prior to entry to the study (excluding placement of vascular access), or minor surgery within 2 weeks of entry into the study.
Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions.
Patients with diabetes type 1 or uncontrolled type II (HbA1c > 8% assessed locally)

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01597388). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.