Postmenopausal Women With ER+ HER2- Primary Breast CancerPhase 1D6090C00002NCT03236974
Study to Compare the Effects of AZD9496 vs Fulvestrant in Breast Cancer.
A Phase 1 study testing Standard Arm - Fulvestrant and AZD9496 in people with Postmenopausal Women With ER+ HER2- Primary Breast Cancer, run by AstraZeneca at 12 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 120 years, women only
- Conditions the study is for
- Postmenopausal Women With ER+ HER2- Primary Breast Cancer
- What is being tested?
- Standard Arm - Fulvestrant and AZD9496
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 5 Oct 2017to 12 Feb 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated informed consent form (ICF)
- Women >=18 years
- Patients with newly diagnosed resectable primary breast cancer scheduled to undergo treatment with curative intent by surgery
- Histologically confirmed invasive breast cancer involving a palpable tumor of any size, or a tumor with an ultrasound assessed diameter of ≥ 1.0 cm
- Any clinical nodal status
- ER+breast cancer
Show all 9Show fewer
- HER2- breast cancer defined as a negative in situ hybridization test or an immno-histochemistry (IHC) status of 0 or 1+
- Eastern Co-operative Oncology group (ECOG) performance status 0-1
- 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
Who cannot join
- Pre-treatment biopsy sample not likely to provide adequate tissue sections for the biomarker assays
- Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
- Inflammatory breast cancer
- Evidence of metastases
- 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
- Concurrent treatment with other experimental drugs within 4 weeks prior to receiving study treatment
Show all 22Show fewer
- Use of hormone-replacement therapy from <4 weeks of the diagnostic/baseline core biopsy to the start of trial treatment
- Patients with second primary cancer. Any endocrine therapies or other anti-cancer therapies must have been ceased at least 12 months prior to enrollment.
- 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
- 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
- As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases,
- Uncontrolled symptomatic thyroid dysfunction (hyperthyroidism or hypothyroidism).
- Unexplained symptomatic endometrial disorders.
- 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.
- 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
- Direct involvement in the planning and conduct of the study
- History of hypersensitivity to AZD9496
- History of hypersensitivity to fulvestrant and/or castor oil
- 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
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United Kingdom8 sites
Research Site
Derby, DE22 3DT
Research Site
Edinburgh, EH4 2XU
Research Site
London, EC1M 6BQ
Research Site
London, SE1 9RT
Research Site
London, W12 0NN
Research Site
Manchester, M23 9LT
Research Site
Poole, BH15 2JB
Research Site
Sutton in Ashfield, NG17 4JL
Germany4 sites
Research Site
Erlangen, 91054
Research Site
Minden, 32429
Research Site
München, 81377
Research Site
Schwerin, 19049
About this study
Official title: 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.
Read the 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.
- Being tested
- Standard Arm - Fulvestrant, AZD9496
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Arm - FulvestrantDrug
Also called Fulvestrant
500 mg Fulvestrant administered as two consecutive 5 ml intramuscular injections on Day 1, one in each buttock
AZD9496Drug
Also called Study drug
Administered at 250 mg bd orally for 5-14 days commencing on Day 1, and continuing up to the day of biopsy
| Study group | Role | What they receive |
|---|---|---|
| Standard arm | Active comparator | Fulvestrant, 500 mg Receives: Drug: Standard Arm - Fulvestrant |
| AZD9496 | Experimental | 250 mg bd taken orally for 5-14 days Receives: Drug: AZD9496 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacodynamics changes to estrogen receptor (ER) expression following treatment with AZD9496 or fulvestrant
Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. ER expression
Measured: 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 outcomes (7)
Pharmacodynamics changes to progesterone receptor (PgR) expression following treatment with AZD9496 or fulvestrant
Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. PgR expression
Measured: 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
Evaluation of AZD9496 and fulvestrant activity in the tumour by assessment of pharmacodynamics biomarker changes i.e. Ki67 protein biomarker expression
Measured: 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
Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data, vital signs and ECG changes.
Measured: From first dose until 28 days after last dose of AZD9496
Safety and tolerability of fulvestrant
Safety and tolerability will be assessed in terms of adverse events (AEs), laboratory data and vital signs
Measured: From first dose until 28 days after fulvestrant
Plasma concentration of AZD9496 - stand alone biopsy visit option
Determination of AZD9496 concentrations in plasma
Measured: 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
Determination of fulvestrant concentration in plasma
Measured: A blood sample will be collected anytime before biopsy.
Plasma concentration of AZD9496 - on the table biopsy option
Determination of AZD9496 concentration in plasma
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2017
- Study start5 Oct 2017
- Primary completion12 Feb 2019
- Study completion12 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Postmenopausal Women With ER+ HER2- Primary Breast CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03236974
- Sponsor's protocol ID
- D6090C00002
- Acronym
- D6090C00002
- Status last verified
- Feb 2020
- First submitted
- 18 Jul 2017
- Last updated
- 6 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Robertson JFR, Evans A, Henschen S, Kirwan CC, Jahan A, Kenny LM, Dixon JM, Schmid P, Kothari A, Mohamed O, Fasching PA, Cheung KL, Wuerstlein R, Carroll D, Klinowska T, Lindemann JPO, MacDonald A, Mather R, Maudsley R, Moschetta M, Nikolaou M, Roudier MP, Sarvotham T, Schiavon G, Zhou D, Zhou L, Harbeck N. A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER+ HER2- Primary Breast Cancer. Clin Cancer Res. 2020 Aug 15;26(16):4242-4249. doi: 10.1158/1078-0432.CCR-19-3387. Epub 2020 Mar 31.
PubMed 32234755
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03236974
- Acronym / sponsor ID
- D6090C00002 / D6090C00002
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 5 Oct 2017 (actual)
- Primary completion
- 12 Feb 2019 (actual)
- Study completion
- 12 Feb 2019 (actual)
- First posted
- 2 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Standard arm | Active comparator | Drug: Standard Arm - FulvestrantFulvestrant, 500 mg |
| AZD9496 | Experimental | Drug: AZD9496250 mg bd taken orally for 5-14 days |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Signed and dated informed consent form (ICF)
- Women >=18 years
- Patients with newly diagnosed resectable primary breast cancer scheduled to undergo treatment with curative intent by surgery
- Histologically confirmed invasive breast cancer involving a palpable tumor of any size, or a tumor with an ultrasound assessed diameter of ≥ 1.0 cm
- Any clinical nodal status
Key exclusion criteria (22 listed)
- Pre-treatment biopsy sample not likely to provide adequate tissue sections for the biomarker assays
- Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments)
- Inflammatory breast cancer
- Evidence of metastases
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard Arm - FulvestrantAlso: Fulvestrant500 mg Fulvestrant administered as two consecutive 5 ml intramuscular injections on Day 1, one in each buttock | Drug | Standard arm |
| AZD9496Also: Study drugAdministered at 250 mg bd orally for 5-14 days commencing on Day 1, and continuing up to the day of biopsy | Drug | AZD9496 |
Primary outcome
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
7 secondary outcomes
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
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
Safety and tolerability of AZD9496
Time frame: 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
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
Plasma concentration of fulvestrant
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2020.
- Derived from this study: PubMed 32234755Robertson JFR, Evans A, Henschen S, Kirwan CC, Jahan A, Kenny LM, Dixon JM, Schmid P, Kothari A, Mohamed O, Fasching PA, Cheung KL, Wuerstlein R, Carroll D, Klinowska T, Lindemann JPO, MacDonald A, Mather R, Maudsley R, Moschetta M, Nikolaou M, Roudier MP, Sarvotham T, Schiavon G, Zhou D, Zhou L, Harbeck N. A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER+ HER2- Primary Breast Cancer. Clin Cancer Res. 2020 Aug 15;26(16):4242-4249. doi: 10.1158/1078-0432.CCR-19-3387. Epub 2020 Mar 31.
- Results of this clinical trial are available on www.astrazenecaclinicaltrials.comLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Standard Arm - Fulvestrant and AZD9496 in people with Postmenopausal Women With ER+ HER2- Primary Breast Cancer, run by AstraZeneca at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United Kingdom, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03236974, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2020.