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

• ClinicalTrials.gov Identifier: NCT01597388
• Recruitment Status: Active, not recruiting
• First Posted: May 14, 2012
• Results First Posted: October 17, 2018
• Last Update Posted: January 24, 2022
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Advanced Metastatic Breast Cancer	Drug: AZD2014; Drug: Fulvestrant	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 99 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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
• Actual Study Start Date: May 8, 2012
• Actual Primary Completion Date: August 4, 2016
• Estimated Study Completion Date: December 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: AZD2014 with Fulvestrant; 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 Name: faslodex

Outcome Measures

Primary Outcome Measures :

1. Adverse Events [ Time Frame: Up to 12 Months ]
2. Adverse Events Leading to Dose Reduction of AZD2014 [ Time Frame: Up to 28 Days ]
3. Clinically Important Changes in Haematology Parameters [ Time Frame: Up to 12 Months ]
4. Clinically Important Changes in Clinical Chemistry Parameters [ Time Frame: Up to 12 Months ]
5. Left Ventricular Ejection Fraction [ Time Frame: 24 hours ]
6. QTcF Over 24 Hours [ Time Frame: 24 hours ]
7. Post-Baseline Glucose Elevation [ Time Frame: 28 Days ]
8. Sitting Diastolic Blood Pressure [ Time Frame: 28 Days ]
9. Sitting Systolic Blood Pressure [ Time Frame: 28 Days ]
10. Respiratory Rate [ Time Frame: 28 Days ]
11. Heart Rate [ Time Frame: 28 Days ]
12. Body Temperature [ Time Frame: 28 Days ]
13. Oxygen Saturation [ Time Frame: 28 Days ]
14. AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant [ Time Frame: 5 Days ]
15. 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 ]
16. 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 ]
17. 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 ]
18. AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-∞) Cycle 0 Days -5 to -1, Continuous Dosing, no Fulvestrant [ Time Frame: 5 Days ]
19. AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 15, BID Intermittent Dosing, With Fulvestrant [ Time Frame: 15 Days ]
20. 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 ]
21. AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 15 Intermittent Dosing, With Fulvestrant [ Time Frame: 15 Days ]
22. AZD2014 Peak Plasma Concentration at Steady State (Cmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant [ Time Frame: 22 Days ]
23. Time to AZD2014 Peak Plasma Concentration at Steady State (Tmax,ss) on Cycle 1 Day 22, Continuous Dosing, With Fulvestrant [ Time Frame: 22 Days ]
24. AZD2014 Area Under the Plasma Concentration Time Curve (AUC 0-12) Cycle 1 Day 22 Continuous Dosing, With Fulvestrant [ Time Frame: 15 Days ]

Secondary Outcome Measures :

1. AZD2014 Peak Plasma Concentration (Cmax) Following Single Dose, Fasted, no Fulvestrant. [ Time Frame: 1 Day ]
2. Time to AZD2014 Peak Plasma Concentration (Tmax) Following Single Dose, Fasted, no Fulvestrant. [ Time Frame: 1 Day ]
3. 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 ]
4. 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 ]
5. 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).
6. 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.
7. 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.
8. 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.
9. 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.
10. Progression Free Survival [ Time Frame: Up to 12 months ]
11. Progression Free Survival at 26 Weeks [ Time Frame: Up to 12 months ]

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, Florida

Research Site

Sarasota, Florida, United States, 34232

United States, Michigan

Research Site

Detroit, Michigan, United States, 48201

United States, Oklahoma

Research Site

Oklahoma City, Oklahoma, United States, 73104

United States, South Carolina

Research Site

Greenville, South Carolina, United States, 29605

United States, Tennessee

Research Site

Nashville, Tennessee, United States, 37203

Sponsors and Collaborators

AstraZeneca

Investigators

• Study Chair: Howard Burris, MD; SCRI Development Innovations, LLC

More Information

Additional Information:

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

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT01597388
• Other Study ID Numbers: D2270C00005; BRE-196
• First Posted: May 14, 2012
• Results First Posted: October 17, 2018
• Last Update Posted: January 24, 2022
• Last Verified: January 2022

Keywords provided by AstraZeneca:

Estrogen receptor positive; Advanced metastatic breast cancer; Estrogen receptor positive advanced metastatic breast cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Fulvestrant; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Estrogen Receptor Antagonists; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs