AZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer
- Conditions
- Advanced Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT01597388
- Lead Sponsor
- AstraZeneca
- Brief Summary
The purpose of this study is to assess safety and tolerability of AZD2014 when given in combination with Fulvestrant
- Detailed Description
A Phase I, Open-label, Multicentre, Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AZD2014 Administered Orally in Combination with Intramuscular (IM) Fulvestrant to Patients with Estrogen Receptor Positive (ER+) Advanced, Metastatic Breast Cancer.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 99
- 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.
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AZD2014 with Fulvestrant AZD2014 AZD2014 with Fulvestrant AZD2014 with Fulvestrant Fulvestrant AZD2014 with Fulvestrant
- Primary Outcome Measures
Name Time Method Post-Baseline Glucose Elevation 28 Days Sitting Diastolic Blood Pressure 28 Days Sitting Systolic Blood Pressure 28 Days Respiratory Rate 28 Days Adverse Events Up to 12 Months Adverse Events Leading to Dose Reduction of AZD2014 Up to 28 Days Clinically Important Changes in Clinical Chemistry Parameters Up to 12 Months AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant 5 Days AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant 5 Days AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant 5 Days AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant 5 Days AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant 5 Days AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant 15 Days Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant 15 Days Clinically Important Changes in Haematology Parameters Up to 12 Months Left Ventricular Ejection Fraction 24 hours QTcF Over 24 Hours 24 hours Heart Rate 28 Days Body Temperature 28 Days Oxygen Saturation 28 Days AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant 22 Days Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant 22 Days AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant 15 Days AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant 15 Days
- Secondary Outcome Measures
Name Time Method AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant. 1 Day Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant. 1 Day Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant. 1 Day Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant. 1 Day Objective Response Rate Up to 12 months Objective Response Rate (ORR) is defined as the number (%) of patients with a confirmed overall response of either complete response (CR) or partial response (PR).
Best Objective Response (BOR) Up to 12 months Best objective response was the best response a patient had following start of treatment but prior to starting any subsequent cancer therapy and prior to RECIST v1.1 progression or the last evaluable assessment in the absence of RECIST v1.1 progression.
Duration of Response (DoR) Up to 12 months Duration of response is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
Clinical Benefit Rate (CBR) at 24 Weeks Up to 12 months The Clinical Benefit Rate (CBR) at 24 weeks is defined as the percentage of patients who had a confirmed BOR of CR or PR in the first 24 weeks or who demonstrated SD for a minimum interval of 24 weeks (minus 1 week to allow for an early assessment within the assessment window, i.e., 161 days) following the start of treatment.
Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size. Up to 12 months Baseline was defined as last evaluable assessment prior to starting treatment. Tumour size was the sum of the longest diameters of the target lesions. TLs are measurable tumour lesions.
Progression Free Survival Up to 12 months Progression Free Survival at 26 Weeks Up to 12 months
Trial Locations
- Locations (1)
Research Site
🇺🇸Nashville, Tennessee, United States