Clinical trial NCT01597388: AZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Metastatic Breast Cancer
Keywords: Estrogen receptor positive
Advanced metastatic breast cancer
Estrogen receptor positive advanced metastatic breast cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-05-14
Enrollment: 99
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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)

Primary outcomes:
measure: Adverse Events
timeFrame: Up to 12 Months
measure: Adverse Events Leading to Dose Reduction of AZD2014
timeFrame: Up to 28 Days
measure: Clinically Important Changes in Haematology Parameters
timeFrame: Up to 12 Months
measure: Clinically Important Changes in Clinical Chemistry Parameters
timeFrame: Up to 12 Months
measure: Left Ventricular Ejection Fraction
timeFrame: 24 hours
measure: QTcF Over 24 Hours
timeFrame: 24 hours
measure: Post-Baseline Glucose Elevation
timeFrame: 28 Days
measure: Sitting Diastolic Blood Pressure
timeFrame: 28 Days
measure: Sitting Systolic Blood Pressure
timeFrame: 28 Days
measure: Respiratory Rate
timeFrame: 28 Days
measure: Heart Rate
timeFrame: 28 Days
measure: Body Temperature
timeFrame: 28 Days
measure: Oxygen Saturation
timeFrame: 28 Days
measure: AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
timeFrame: 5 Days
measure: AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
timeFrame: 5 Days
measure: AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
timeFrame: 5 Days
measure: AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
timeFrame: 5 Days
measure: AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
timeFrame: 5 Days
measure: AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
timeFrame: 15 Days
measure: Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
timeFrame: 15 Days
measure: AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant
timeFrame: 15 Days
measure: AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
timeFrame: 22 Days
measure: Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
timeFrame: 22 Days
measure: AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant
timeFrame: 15 Days
Secondary outcomes:
measure: AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.
timeFrame: 1 Day
measure: Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.
timeFrame: 1 Day
measure: Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.
timeFrame: 1 Day
measure: Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.
timeFrame: 1 Day
measure: Objective Response Rate
timeFrame: Up to 12 months
measure: Best Objective Response (BOR)
timeFrame: Up to 12 months
measure: Duration of Response (DoR)
timeFrame: Up to 12 months
measure: Clinical Benefit Rate (CBR) at 24 Weeks
timeFrame: Up to 12 months
measure: Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.
timeFrame: Up to 12 months
measure: Progression Free Survival
timeFrame: Up to 12 months
measure: Progression Free Survival at 26 Weeks
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Research Site
state: Florida
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Nashville
country: United States
facility: Research Site
state: Tennessee
Study officials:
References: