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

Advanced Metastatic Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01597388
• Other study ID #: D2270C00005
• Secondary ID: BRE-196264477
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 8, 2012
• Est. completion date: September 5, 2028

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess safety and tolerability of AZD2014 when given in combination with Fulvestrant

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 99
• Est. completion date: September 5, 2028
• Est. primary completion date: August 4, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

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)

Related Conditions & MeSH terms

• Advanced Metastatic Breast Cancer
• Breast Neoplasms

Intervention

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
• Fulvestrant
IM monthly after loading dose

Locations

Country	Name	City	State
United States	Research Site	Detroit	Michigan
United States	Research Site	Greenville	South Carolina
United States	Research Site	Nashville	Tennessee
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events		Up to 12 Months
Primary	Adverse Events Leading to Dose Reduction of AZD2014		Up to 28 Days
Primary	Clinically Important Changes in Haematology Parameters		Up to 12 Months
Primary	Clinically Important Changes in Clinical Chemistry Parameters		Up to 12 Months
Primary	Left Ventricular Ejection Fraction		24 hours
Primary	QTcF Over 24 Hours		24 hours
Primary	Post-Baseline Glucose Elevation		28 Days
Primary	Sitting Diastolic Blood Pressure		28 Days
Primary	Sitting Systolic Blood Pressure		28 Days
Primary	Respiratory Rate		28 Days
Primary	Heart Rate		28 Days
Primary	Body Temperature		28 Days
Primary	Oxygen Saturation		28 Days
Primary	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant		5 Days
Primary	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant		5 Days
Primary	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant		5 Days
Primary	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant		5 Days
Primary	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-8) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant		5 Days
Primary	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant		15 Days
Primary	Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant		15 Days
Primary	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant		15 Days
Primary	AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant		22 Days
Primary	Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant		22 Days
Primary	AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant		15 Days
Secondary	AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.		1 Day
Secondary	Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.		1 Day
Secondary	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
Secondary	Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-8) Following Single Dose, Fasted, no Fulvestrant.		1 Day
Secondary	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).	Up to 12 months
Secondary	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.	Up to 12 months
Secondary	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.	Up to 12 months
Secondary	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.	Up to 12 months
Secondary	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.	Up to 12 months
Secondary	Progression Free Survival		Up to 12 months
Secondary	Progression Free Survival at 26 Weeks		Up to 12 months

External Links

•   AstraZeneca Cancer Study Locator Service http://www.emergingmed.com/networks/AstraZeneca astrazeneca@emergingmed.com 1-877-400-4656