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

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

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 99 participants
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 17, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Fulvestrant

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




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 ]


Information from the National Library of Medicine

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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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01597388


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

Additional Information:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01597388     History of Changes
Other Study ID Numbers: D2270C00005
BRE-196
First Posted: May 14, 2012    Key Record Dates
Results First Posted: October 17, 2018
Last Update Posted: October 17, 2018
Last Verified: October 2018

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
Estrogens
Estradiol
Fulvestrant
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists