Back to resultsAZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer
Primary Purpose
Advanced Metastatic Breast Cancer
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AZD2014
Fulvestrant
Sponsored by
About this trial
This is an interventional basic science trial for Advanced Metastatic Breast Cancer focused on measuring Estrogen receptor positive, Advanced metastatic breast cancer, Estrogen receptor positive 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)
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
AZD2014 with Fulvestrant
Arm Description
AZD2014 with Fulvestrant
Outcomes
Primary Outcome Measures
Adverse Events
Adverse Events Leading to Dose Reduction of AZD2014
Clinically Important Changes in Haematology Parameters
Clinically Important Changes in Clinical Chemistry Parameters
Left Ventricular Ejection Fraction
QTcF Over 24 Hours
Post-Baseline Glucose Elevation
Sitting Diastolic Blood Pressure
Sitting Systolic Blood Pressure
Respiratory Rate
Heart Rate
Body Temperature
Oxygen Saturation
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant
Secondary Outcome Measures
AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.
Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.
Objective Response Rate
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)
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)
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
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.
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
Progression Free Survival at 26 Weeks
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01597388
Brief Title
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
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 8, 2012 (Actual)
Primary Completion Date
August 4, 2016 (Actual)
Study Completion Date
December 29, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Metastatic Breast Cancer
Keywords
Estrogen receptor positive, Advanced metastatic breast cancer, Estrogen receptor positive advanced metastatic breast cancer
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
99 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD2014 with Fulvestrant
Arm Type
Experimental
Arm Description
AZD2014 with Fulvestrant
Intervention Type
Drug
Intervention Name(s)
AZD2014
Intervention Description
Single dose followed by multiple dosing or twice daily dosing for 2 days folllowed by 5 days off each week, or twice daily dosing on the first and fourth day of the week
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Other Intervention Name(s)
faslodex
Intervention Description
IM monthly after loading dose
Primary Outcome Measure Information:
Title
Adverse Events
Time Frame
Up to 12 Months
Title
Adverse Events Leading to Dose Reduction of AZD2014
Time Frame
Up to 28 Days
Title
Clinically Important Changes in Haematology Parameters
Time Frame
Up to 12 Months
Title
Clinically Important Changes in Clinical Chemistry Parameters
Time Frame
Up to 12 Months
Title
Left Ventricular Ejection Fraction
Time Frame
24 hours
Title
QTcF Over 24 Hours
Time Frame
24 hours
Title
Post-Baseline Glucose Elevation
Time Frame
28 Days
Title
Sitting Diastolic Blood Pressure
Time Frame
28 Days
Title
Sitting Systolic Blood Pressure
Time Frame
28 Days
Title
Respiratory Rate
Time Frame
28 Days
Title
Heart Rate
Time Frame
28 Days
Title
Body Temperature
Time Frame
28 Days
Title
Oxygen Saturation
Time Frame
28 Days
Title
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Time Frame
5 Days
Title
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Time Frame
5 Days
Title
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Time Frame
5 Days
Title
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Time Frame
5 Days
Title
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Time Frame
5 Days
Title
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
Time Frame
15 Days
Title
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
Time Frame
15 Days
Title
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant
Time Frame
15 Days
Title
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
Time Frame
22 Days
Title
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
Time Frame
22 Days
Title
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant
Time Frame
15 Days
Secondary Outcome Measure Information:
Title
AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.
Time Frame
1 Day
Title
Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.
Time Frame
1 Day
Title
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.
Time Frame
1 Day
Title
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.
Time Frame
1 Day
Title
Objective Response Rate
Description
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).
Time Frame
Up to 12 months
Title
Best Objective Response (BOR)
Description
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.
Time Frame
Up to 12 months
Title
Duration of Response (DoR)
Description
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.
Time Frame
Up to 12 months
Title
Clinical Benefit Rate (CBR) at 24 Weeks
Description
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.
Time Frame
Up to 12 months
Title
Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.
Description
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.
Time Frame
Up to 12 months
Title
Progression Free Survival
Time Frame
Up to 12 months
Title
Progression Free Survival at 26 Weeks
Time Frame
Up to 12 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
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)
Facility Information:
Facility Name
Research Site
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Research Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Research Site
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Research Site
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.emergingmed.com/networks/AstraZeneca
Description
AstraZeneca Cancer Study Locator Service http://www.emergingmed.com/networks/AstraZeneca astrazeneca@emergingmed.com 1-877-400-4656
Learn more about this trial
AZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer
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