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

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ClinicalTrials.gov Identifier: NCT01597388
Recruitment Status : Active, not recruiting
First Posted : May 14, 2012
Results First Posted : October 17, 2018
Last Update Posted : October 17, 2018
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

March 28, 2012
May 14, 2012
September 18, 2017
October 17, 2018
October 17, 2018
May 8, 2012
August 4, 2016   (Final data collection date for primary outcome measure)
  • Adverse Events [ Time Frame: Up to 12 Months ]
  • Adverse Events Leading to Dose Reduction of AZD2014 [ Time Frame: Up to 28 Days ]
  • Clinically Important Changes in Haematology Parameters [ Time Frame: Up to 12 Months ]
  • Clinically Important Changes in Clinical Chemistry Parameters [ Time Frame: Up to 12 Months ]
  • Left Ventricular Ejection Fraction [ Time Frame: 24 hours ]
  • QTcF Over 24 Hours [ Time Frame: 24 hours ]
  • Post-Baseline Glucose Elevation [ Time Frame: 28 Days ]
  • Sitting Diastolic Blood Pressure [ Time Frame: 28 Days ]
  • Sitting Systolic Blood Pressure [ Time Frame: 28 Days ]
  • Respiratory Rate [ Time Frame: 28 Days ]
  • Heart Rate [ Time Frame: 28 Days ]
  • Body Temperature [ Time Frame: 28 Days ]
  • Oxygen Saturation [ Time Frame: 28 Days ]
  • AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant [ Time Frame: 5 Days ]
  • 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 ]
  • 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 ]
  • 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 ]
  • AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant [ Time Frame: 5 Days ]
  • AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant [ Time Frame: 15 Days ]
  • 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 ]
  • AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant [ Time Frame: 15 Days ]
  • AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant [ Time Frame: 22 Days ]
  • Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant [ Time Frame: 22 Days ]
  • AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant [ Time Frame: 15 Days ]
  • To assess safety and tolerability of AZD2014, when given in combination with fulvestrant, by assessment of: adverse events, clinical chemistry and haematology laboratory parameters, ECG data, vital signs and physical examination. [ Time Frame: From screening until the end of the follow up period, an expected average of 6 months ]
  • To determine the steady state PK profile of AZD2014 in combination with fulvestrant by assessment including:maximum plasma concentration of AZD2014 at steady state(Css,max),time to Css,max and area under the plasma concentration-time curve (AUCss). [ Time Frame: At multiple time-points on Day 22 of multiple dosing ]
Complete list of historical versions of study NCT01597388 on ClinicalTrials.gov Archive Site
  • AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant. [ Time Frame: 1 Day ]
  • Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant. [ Time Frame: 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. [ Time Frame: 1 Day ]
  • 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 ]
  • Objective Response Rate [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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. [ Time Frame: 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 [ Time Frame: Up to 12 months ]
  • Progression Free Survival at 26 Weeks [ Time Frame: Up to 12 months ]
  • To determine the minimum plasma concentration at steady state of fulvestrant when administered in combination with AZD2014. [ Time Frame: Samples will be obtained on Day 29 and Day 57 of multiple dosing ]
  • To determine the single dose PK profile of AZD2014,by assessments including: maximum plasma concentration (Cmax),time to Cmax,terminal rate constant half life,area under the plasma concentration-time curve (AUC0-12 and AUC0-24). [ Time Frame: At multiple time-points on the day of single dosing. This will be up to 5 days prior to the start of multiple dosing. ]
Not Provided
Not Provided
 
AZD2014 and Fulvestrant in Patients With ER+ Advanced Metastatic Breast Cancer
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
The purpose of this study is to assess safety and tolerability of AZD2014 when given in combination with Fulvestrant.
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.
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Advanced Metastatic Breast Cancer
  • Drug: 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
  • Drug: Fulvestrant
    IM monthly after loading dose
    Other Name: faslodex
Experimental: AZD2014 with Fulvestrant
AZD2014 with Fulvestrant
Interventions:
  • Drug: AZD2014
  • Drug: Fulvestrant
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
99
30
December 17, 2018
August 4, 2016   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: Female
18 Years to 100 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01597388
D2270C00005
BRE-196
Not Provided
Not Provided
Not Provided
AstraZeneca
AstraZeneca
Not Provided
Study Chair: Howard Burris, MD SCRI Development Innovations, LLC
AstraZeneca
October 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP