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

AstraZeneca99 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Advanced Metastatic Breast Cancer

Interventions

AZD2014DRUG

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

FulvestrantDRUG

IM monthly after loading dose

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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)

Locations (5)

Research Site

Sarasota, Florida, United States

Research Site

Detroit, Michigan, United States

Research Site

Oklahoma City, Oklahoma, United States

Research Site

Greenville, South Carolina, United States

Outcomes

Primary Outcomes

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

Data from ClinicalTrials.gov

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Secondary Outcomes

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

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

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 12 months

Progression Free Survival

Time frame: Up to 12 months

Progression Free Survival at 26 Weeks

Time frame: Up to 12 months