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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by AstraZeneca
Information provided by (Responsible Party):
AstraZeneca Identifier:
First received: March 28, 2012
Last updated: March 23, 2015
Last verified: March 2015

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

Condition Intervention Phase
Advanced Metastatic Breast Cancer
Drug: AZD2014
Drug: Fulvestrant
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Assessment of 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 ] [ Designated as safety issue: Yes ]
  • Determination of the steady state/multiple dose PK profile of AZD2014 in combination with fulvestrant by assessments including:maximum plasma concentration of AZD2014 (Cmax),time to Cmax and area under the plasma concentration-time curve (AUC). [ Time Frame: At multiple time-points on Day 22 of multiple continuous dosing, Day 23 of intermittent Day 1 and 2 dosing or the fourth day of intermittent Day 1 and 4 dosing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Determination of 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 ] [ Designated as safety issue: No ]
  • Determination of 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: for continuous dosing, on the day of single dosing (up to 5 days prior to the start of multiple dosing); for Day 1 & 2 intermittent, on the first dose of week 3; for Day 1 & 4 intermittent, on the first day of dosing. ] [ Designated as safety issue: No ]
  • Obtain a preliminary assessment of the anti-tumour activity of AZD2014, when given in combination with fulvestrant, by evaluation of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST Version 1.1) [ Time Frame: At screening and every 8 weeks until progression, an expected average of 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 122
Study Start Date: May 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01597388

Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479
Contact: ASKSARAH Dedicated Service for our Patients and Research Sites 1-877-MY-1-SCRI (691-7274)

United States, Florida
Research Site Recruiting
Sarasota, Florida, United States
United States, Michigan
Research Site Recruiting
Detroit, Michigan, United States
United States, South Carolina
Research Site Recruiting
Greenville, South Carolina, United States
United States, Tennessee
Research Site Recruiting
Nashville, Tennessee, United States
Sponsors and Collaborators
Study Chair: Howard Burris, MD SCRI Development Innovations, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca Identifier: NCT01597388     History of Changes
Other Study ID Numbers: D2270C00005, BRE-196
Study First Received: March 28, 2012
Last Updated: March 23, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Estrogen receptor positive
Advanced metastatic breast cancer
Estrogen receptor positive advanced metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on March 26, 2015