Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01597388




Registration number
NCT01597388
Ethics application status
Date submitted
28/03/2012
Date registered
14/05/2012
Date last updated
1/10/2024

Titles & IDs
Public title
AZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer
Scientific 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
Secondary ID [1] 0 0
BRE-196
Secondary ID [2] 0 0
D2270C00005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD2014
Treatment: Drugs - Fulvestrant

Experimental: AZD2014 with Fulvestrant - AZD2014 with Fulvestrant


Treatment: Drugs: AZD2014
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

Treatment: Drugs: Fulvestrant
IM monthly after loading dose
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events
Timepoint [1] 0 0
Up to 12 Months
Primary outcome [2] 0 0
Adverse Events Leading to Dose Reduction of AZD2014
Timepoint [2] 0 0
Up to 28 Days
Primary outcome [3] 0 0
Clinically Important Changes in Haematology Parameters
Timepoint [3] 0 0
Up to 12 Months
Primary outcome [4] 0 0
Clinically Important Changes in Clinical Chemistry Parameters
Timepoint [4] 0 0
Up to 12 Months
Primary outcome [5] 0 0
Left Ventricular Ejection Fraction
Timepoint [5] 0 0
24 hours
Primary outcome [6] 0 0
QTcF Over 24 Hours
Timepoint [6] 0 0
24 hours
Primary outcome [7] 0 0
Post-Baseline Glucose Elevation
Timepoint [7] 0 0
28 Days
Primary outcome [8] 0 0
Sitting Diastolic Blood Pressure
Timepoint [8] 0 0
28 Days
Primary outcome [9] 0 0
Sitting Systolic Blood Pressure
Timepoint [9] 0 0
28 Days
Primary outcome [10] 0 0
Respiratory Rate
Timepoint [10] 0 0
28 Days
Primary outcome [11] 0 0
Heart Rate
Timepoint [11] 0 0
28 Days
Primary outcome [12] 0 0
Body Temperature
Timepoint [12] 0 0
28 Days
Primary outcome [13] 0 0
Oxygen Saturation
Timepoint [13] 0 0
28 Days
Primary outcome [14] 0 0
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Timepoint [14] 0 0
5 Days
Primary outcome [15] 0 0
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Timepoint [15] 0 0
5 Days
Primary outcome [16] 0 0
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Timepoint [16] 0 0
5 Days
Primary outcome [17] 0 0
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Timepoint [17] 0 0
5 Days
Primary outcome [18] 0 0
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-8) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant
Timepoint [18] 0 0
5 Days
Primary outcome [19] 0 0
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
Timepoint [19] 0 0
15 Days
Primary outcome [20] 0 0
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant
Timepoint [20] 0 0
15 Days
Primary outcome [21] 0 0
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant
Timepoint [21] 0 0
15 Days
Primary outcome [22] 0 0
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
Timepoint [22] 0 0
22 Days
Primary outcome [23] 0 0
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant
Timepoint [23] 0 0
22 Days
Primary outcome [24] 0 0
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant
Timepoint [24] 0 0
15 Days
Secondary outcome [1] 0 0
AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.
Timepoint [1] 0 0
1 Day
Secondary outcome [2] 0 0
Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.
Timepoint [2] 0 0
1 Day
Secondary outcome [3] 0 0
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to 12 Hours (AUC 0-12) Following Single Dose, Fasted, no Fulvestrant.
Timepoint [3] 0 0
1 Day
Secondary outcome [4] 0 0
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-8) Following Single Dose, Fasted, no Fulvestrant.
Timepoint [4] 0 0
1 Day
Secondary outcome [5] 0 0
Objective Response Rate
Timepoint [5] 0 0
Up to 12 months
Secondary outcome [6] 0 0
Best Objective Response (BOR)
Timepoint [6] 0 0
Up to 12 months
Secondary outcome [7] 0 0
Duration of Response (DoR)
Timepoint [7] 0 0
Up to 12 months
Secondary outcome [8] 0 0
Clinical Benefit Rate (CBR) at 24 Weeks
Timepoint [8] 0 0
Up to 12 months
Secondary outcome [9] 0 0
Percentage Change From Baseline at 16 Weeks in Target Lesion (TL) Size.
Timepoint [9] 0 0
Up to 12 months
Secondary outcome [10] 0 0
Progression Free Survival
Timepoint [10] 0 0
Up to 12 months
Secondary outcome [11] 0 0
Progression Free Survival at 26 Weeks
Timepoint [11] 0 0
Up to 12 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
100 Years
Sex
Females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/05/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
5/09/2028
Actual
Sample size
Target
Accrual to date
Final
99
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
Oklahoma
Country [4] 0 0
United States of America
State/province [4] 0 0
South Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess safety and tolerability of AZD2014 when given in combination with Fulvestrant
Trial website
https://clinicaltrials.gov/study/NCT01597388
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01597388