Study to Compare the Effects of AZD9496 vs Fulvestrant in Breast Cancer. (D6090C00002)

February 5, 2020 updated by: AstraZeneca

An Open Label, Randomised, Pre-surgical, Pharmacodynamics Study to Compare the Biological Effects of AZD9496 Versus Fulvestrant in Postmenopausal Women With ER Positive HER-2 Negative Primary Breast Cancer

This is an open label randomised multicentre pre-surgical pharmacodynamics study to compare and assess the biological effects of AZD9496 and fulvestrant in postmenopausal women with estrogen receptor (ER) positive (ER+), human epidermal growth factor receptor 2 (HER-2) negative (HER2-) primary breast cancer.

Patients will receive AZD9496 or fulvestrant and will have an on-treatment image

-guided core biopsy after 5-14 days of commencing treatment.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open label, randomized, multi-centre study in postmenopausal women with primary ER+ HER2- breast cancer. Patients will be randomised to an oral dose of 250 mg bd AZD9496 or 500mg fulvestrant i.m. administered on one occasion. Patients diagnosed with primary breast cancer who are scheduled for surgery with curative intent will be consented to the study including consent to use the formalin fixed paraffin embedded (FFPE) diagnostic tumor biopsy sample and fresh frozen tumor biopsy sample (if available) for research purposes. Patients may also consent to provide an optional pretreatment fresh frozen tumor biopsy sample if this was not obtained at the time of initial diagnostic biopsy. If the diagnostic biopsy was taken ≥ 6 weeks prior to starting treatment or was not of sufficient quality, new tumor core biopsies (FFPE and fresh frozen) must be taken. Following the screening visit, eligible patients will be randomised to receive one of the following study treatments:

  • AZD9496 administered at 250 mg bd orally for 5-14 days commencing on Day 1, and continuing up to the day of biopsy OR
  • fulvestrant 500 mg administered as two consecutive 5 ml intramuscular injections on Day 1, one in each buttock.

After the morning dose of AZD9496 on the day of biopsy dosing will be stopped. If following initiation of AZD9496 treatment, dosing will be stopped if biopsy is postponed beyond Day 14. Patients will be considered not evaluable for the study if biopsy is postponed beyond day 14 of AZD9496/fulvestrant treatment initiation. Core tumor biopsies will be taken at either the time of definitive surgery or at a separate visit prior to surgery in the period between (and including) day 5 and day 14. Subjects who are scheduled to start a subsequent neoadjuvant therapy must have their core tumor biopsies performed before commencing neoadjuvant treatment.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Erlangen, Germany, 91054
        • Research Site
      • Minden, Germany, 32429
        • Research Site
      • München, Germany, 81377
        • Research Site
      • Schwerin, Germany, 19049
        • Research Site
  • United Kingdom
      • Derby, United Kingdom, DE22 3DT
        • Research Site
      • Edinburgh, United Kingdom, EH4 2XU
        • Research Site
      • London, United Kingdom, SE1 9RT
        • Research Site
      • London, United Kingdom, EC1M 6BQ
        • Research Site
      • London, United Kingdom, W12 0NN
        • Research Site
      • Manchester, United Kingdom, M23 9LT
        • Research Site
      • Poole, United Kingdom, BH15 2JB
        • Research Site
      • Sutton In Ashfield, United Kingdom, NG17 4JL
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion criteria:

  1. Signed and dated informed consent form (ICF)
  2. Women >=18 years
  3. Patients with newly diagnosed resectable primary breast cancer scheduled to undergo treatment with curative intent by surgery
  4. Histologically confirmed invasive breast cancer involving a palpable tumor of any size, or a tumor with an ultrasound assessed diameter of ≥ 1.0 cm
  5. Any clinical nodal status
  6. ER+breast cancer
  7. HER2- breast cancer defined as a negative in situ hybridization test or an immno-histochemistry (IHC) status of 0 or 1+
  8. Eastern Co-operative Oncology group (ECOG) performance status 0-1
  9. Post-menopausal status defined as meeting at least one of the following criteria: Have undergone a bilateral oophorectomy; Age ≥60 years; Age ≥50 years and with cessation of regular menses ≥12 months and with an intact uterus in the absence of oral contraception or hormone-replacement therapy (HRT) prior to the diagnosis of breast cancer; Age <60 years and with cessation of regular menses ≥12 months and follicle stimulating hormone (FSH) and oestradiol levels in the postmenopausal range

Exclusion criteria:

  1. Pre-treatment biopsy sample not likely to provide adequate tissue sections for the biomarker assays
  2. Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
  3. Inflammatory breast cancer
  4. Evidence of metastases
  5. Patients currently receiving medications or herbal supplements known to be strong inhibitors/inducers of CYP3A4/5 or strong inhibitors of CYP2C8 or that are sensitive substrates of CYP2C8 inhibition
  6. Concurrent treatment with other experimental drugs within 4 weeks prior to receiving study treatment
  7. Use of hormone-replacement therapy from <4 weeks of the diagnostic/baseline core biopsy to the start of trial treatment
  8. Patients with second primary cancer. Any endocrine therapies or other anti-cancer therapies must have been ceased at least 12 months prior to enrollment.

  9. Any of the following cardiac criteria:

    • Mean resting QT interval corrected for heart rate (QTc) > 470 msec obtained from 3 ECGs using Fridericia's formula
    • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG
    • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events
  10. Experience of any of the following in the preceding 6 months: coronary artery bypass graft (CABG), angioplasty, vascular stent, myocardial infarction (MI), angina pectoris, congestive heart failure New York Heart Association (NYHA) Grade ≥2, cerebrovascular accident (CVA), transient ischaemic attack (TIA), deep venous or arterial thrombosis, pulmonary embolism, bleeding diathesis (i.e., disseminated intravascular coagulation, clotting factor deficiency) or requirement of anticoagulant therapy
  11. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases,
  12. Uncontrolled symptomatic thyroid dysfunction (hyperthyroidism or hypothyroidism).
  13. Unexplained symptomatic endometrial disorders.
  14. Refractory nausea and vomiting, uncontrolled chronic GI diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9496.
  15. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values: absolute neutrophil count < 1.5 x 109/L, Platelet count < 100 x 109/L, Haemoglobin < 90 g/L, alanine aminotransferase (ALT) > 2.5x upper limit of normal (ULN), aspartate aminotransferase (AST) > 2.5 x ULN, Total bilirubin > 1.5 x ULN or > 3 x in case of Gilbert's Syndrome, glomerular filtration rate < 50 mL/min
  16. Direct involvement in the planning and conduct of the study
  17. History of hypersensitivity to AZD9496
  18. History of hypersensitivity to fulvestrant and/or castor oil
  19. Judgment by the investigator that the patient should not participate in the study if unlikely to comply with study procedures, restrictions and requirements In addition, the following is considered a criterion for exclusion from the exploratory genetic research: Previous allogeneic bone marrow transplant; Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard arm
Fulvestrant, 500 mg
Drug: Standard Arm - Fulvestrant
500 mg Fulvestrant administered as two consecutive 5 ml intramuscular injections on Day 1, one in each buttock
Other Names:
  • Fulvestrant
Experimental: AZD9496
250 mg bd taken orally for 5-14 days
Drug: AZD9496
Administered at 250 mg bd orally for 5-14 days commencing on Day 1, and continuing up to the day of biopsy
Other Names:
  • Study drug

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pharmacodynamics changes to estrogen receptor (ER) expression following treatment with AZD9496 or fulvestrant
Time Frame: Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment
Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. ER expression
Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pharmacodynamics changes to progesterone receptor (PgR) expression following treatment with AZD9496 or fulvestrant
Time Frame: Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment
Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. PgR expression
Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment
Pharmacodynamics changes to Ki67 protein biomarker expression following treatment with AZD9496 or fulvestrant
Time Frame: Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment
Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. Ki67 protein biomarker expression
Tumour biopsy taken at baseline within 6 weeks of planned start of study treatment; on-treatment tumour biopsy taken following 5-14 day on study treatment
Safety and tolerability of AZD9496
Time Frame: From first dose until 28 days after last dose of AZD9496
Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data, vital signs and ECG changes.
From first dose until 28 days after last dose of AZD9496
Safety and tolerability of fulvestrant
Time Frame: From first dose until 28 days after fulvestrant
Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data and vital signs
From first dose until 28 days after fulvestrant
Plasma concentration of AZD9496 - stand alone biopsy visit option
Time Frame: Blood samples collected close as possible to time of biopsy, 1-2 hours after biopsy and optional 3-4 hours after biopsy
Determination of AZD9496 concentrations in plasma
Blood samples collected close as possible to time of biopsy, 1-2 hours after biopsy and optional 3-4 hours after biopsy
Plasma concentration of fulvestrant
Time Frame: A blood sample will be collected anytime before biopsy.
Determination of fulvestrant concentration in plasma
A blood sample will be collected anytime before biopsy.
Plasma concentration of AZD9496 - on the table biopsy option
Time Frame: Blood samples collected close as possible to time of biopsy, at least 2 hours after biopsy and 8-12 hours after last dose or at discharge which is defined as up to 12 hours after last dose
Determination of AZD9496 concentration in plasma
Blood samples collected close as possible to time of biopsy, at least 2 hours after biopsy and 8-12 hours after last dose or at discharge which is defined as up to 12 hours after last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 5, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 12, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 12, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 18, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 1, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 2, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 6, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 5, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D6090C00002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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