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

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Metastatic Breast Cancer
• Intervention / Treatment: Drug: AZD2014; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Sarasota, Florida, United States, 34232
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Research Site
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD2014 with Fulvestrant	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 Names: faslodex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse Events	Up to 12 Months
Adverse Events Leading to Dose Reduction of AZD2014	Up to 28 Days
Clinically Important Changes in Haematology Parameters	Up to 12 Months
Clinically Important Changes in Clinical Chemistry Parameters	Up to 12 Months
Left Ventricular Ejection Fraction	24 hours
QTcF Over 24 Hours	24 hours
Post-Baseline Glucose Elevation	28 Days
Sitting Diastolic Blood Pressure	28 Days
Sitting Systolic Blood Pressure	28 Days
Respiratory Rate	28 Days
Heart Rate	28 Days
Body Temperature	28 Days
Oxygen Saturation	28 Days
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-24) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-t) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant	5 Days
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	15 Days
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant	15 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant	15 Days
AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	22 Days
Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant	22 Days
AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant	15 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant.		1 Day
Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant.		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.		1 Day
Area Under the Plasma Concentration-time Curve for AZD2014 From 0 to Infinity (AUC 0-∞) Following Single Dose, Fasted, no Fulvestrant.		1 Day
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
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
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
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
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
Progression Free Survival		Up to 12 months
Progression Free Survival at 26 Weeks		Up to 12 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2012
• Primary Completion (Actual): August 4, 2016
• Study Completion (Estimated): September 5, 2028

Study Registration Dates

• First Submitted: March 28, 2012
• First Submitted That Met QC Criteria: May 10, 2012
• First Posted (Estimated): May 14, 2012

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Estrogen receptor positive; Advanced metastatic breast cancer; Estrogen receptor positive advanced metastatic breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant
• Other Study ID Numbers: D2270C00005; 264477 (Other Identifier: Parexel International (IRL) Limited); BRE-196