ER+ HER2- Advanced Breast CancerPhase 1NCT02248090
AZD9496 First Time in Patients Ascending Dose Study
A Phase 1 study testing AZD9496 in people with ER+ HER2- Advanced Breast Cancer, run by AstraZeneca at 6 sites in 3 countries.
Trial summary
This is a phase 1 open label multicentre study of AZD9496 administered orally in patients with advanced ER+ HER2 negative breast cancer. The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of patients. The study will determine the maximum tolerated dose. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- ER+ HER2- Advanced Breast Cancer
- What is being tested?
- AZD9496
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 6 sitesin 3 countries
- Study dates
- 22 Oct 2014to 3 Apr 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Inclusion Criteria: Provision of signed and dated, written informed consent prior to any mandatory study specific procedures, sampling and analyses. Aged at least 18 years. Any menopausal status. Pre- or peri-menopausal women must have commenced treatment with an LHRH agonist at least 4 weeks prior to starting study treatment and must be willing to continue to receive LHRH agonist therapy for the duration of the trial. Histological or cytological confirmation of adenocarcinoma of the breast. ER-positive according to local laboratory; HER-2 negative. Metastatic disease or locoregionally recurrent disease which is not amenable to treatment with curative intent. Disease progression after at least 6 months of endocrine therapy for ER+ breast cancer. Radiological or objective evidence of progression on or after the last systemic therapy prior to starting study treatment. Receipt of ≤2 lines of prior chemotherapy for advanced disease. Females of child-bearing potential must agree to use adequate contraceptive measures, must not be breast feeding and must have a negative pregnancy test prior to start of dosing. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.
Exclusion Criteria: Any cytotoxic chemotherapy, investigational agents or other anti-cancer drugs for the treatment of advanced breast cancer from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia. Presence of life-threatening metastatic visceral disease, uncontrolled central nervous system metastatic disease or symptomatic pulmonary lymphangitic spread. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or active infection. Unexplained symptomatic endometrial disorders. Uncontrolled symptomatic thyroid dysfunction. Inadequate bone marrow reserve or organ function
Trial locations and contacts
6 sites in 3 countries.
6 sites in 3 countries
United States3 sites
Sarah Cannon
Nashville, Tennessee, 37203
Research Site
New York, New York, 10065
Florida Cancer Specialists
Sarasota, Florida, 34232
United Kingdom2 sites
Research Site
Cambridge, CB2 0QQ
Christie
Manchester, M20 4BX
About this study
Official title: Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD9496 in Women With Estrogen Receptor Positive HER-2 Negative Advanced Breast Cancer
This is a phase 1 open label multicentre study of AZD9496 administered orally in patients with advanced ER+ HER2 negative breast cancer. The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of patients. The study will determine the maximum tolerated dose. In addition, expansion cohort(s) at potential therapeutic dose(s) in patients with or without ESR1 mutations will be enrolled to further determine the safety, tolerability, pharmacokinetics and biological activity of AZD9496
Read the detailed description
A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD9496 in Women with Estrogen Receptor Positive HER-2 Negative Advanced Breast Cancer
- Conditions
- ER+ HER2- Advanced Breast Cancer
- Being tested
- AZD9496
- Keywords
- Phase 1, Safety, Tolerability, Pharmacokinetics, Ascending Doses, Estrogen Receptor Positive, Her2 Negative, Advanced Breast Cancer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD9496Drug
AZD9496
AZD9496Drug
If initial dosing of AZD9496 is tolerated then subsequent cohorts will test increasing doses until a maximum tolerated dose or maximum feasible dose is defined
| Study group | Role | What they receive |
|---|---|---|
| AZD9496 | Experimental | AZD9496 dose escalation and expansion(s) Receives: Drug: AZD9496 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability
Safety and tolerability in terms of adverse events, serious adverse events (including death) and safety measures: ECG, physical examination, vital signs and laboratory variables. Definition of maximum tolerated dose (MTD) or maximum feasible dose (MFD) by measuring the number of evaluable patients with dose-limiting toxicities.Time frame DLT period 28 days
Measured: Routine safety assessments, throughout the period that patients receive AZD9496 up to 28 days following discontinuation of last dose of study treatment.
Secondary outcomes (3)
Single and multiple dose pharmacokinetics of AZD9496
measurement of plasma levels of AZD9496 at pre-defined intervals in order to establish pharmacokinetic parameters
Measured: 12 weeks
4β-hydroxycholesterol concentration in blood
Understanding of the CYP3A4 induction potential of AZD9496 by measuring 4β-hydroxycholesterol concentration in blood samples at pre-defined intervals
Measured: 12 weeks
Antitumour activity
Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
Measured: every 8 weeks for 24 weeks and then every 12 weeks thereafter until disease progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2014 (estimated)
- Study start22 Oct 2014
- Primary completion31 Jan 2017
- Study completion3 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ER+ HER2- Advanced 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Erika Hamilton, Principal investigator, Nashville Hospital, United StatesJustin Lindemann, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02248090
- Sponsor's protocol ID
- D6090C00001
- Status last verified
- Jun 2019
- First submitted
- 22 Sep 2014
- Last updated
- 24 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD9496 in Women With Estrogen Receptor Positive HER-2 Negative Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT02248090
- Acronym / sponsor ID
- D6090C00001
- Conditions
- ER+ HER2- Advanced Breast Cancer
- Keywords
- Phase 1, Safety, Tolerability, Pharmacokinetics, Ascending Doses, Estrogen Receptor Positive, Her2 Negative, Advanced Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 22 Oct 2014 (actual)
- Primary completion
- 31 Jan 2017 (actual)
- Study completion
- 3 Apr 2019 (actual)
- First posted
- 25 Sep 2014 (estimated)
- 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 a phase 1 open label multicentre study of AZD9496 administered orally in patients with advanced ER+ HER2 negative breast cancer. The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of patients. The study will determine the maximum tolerated dose. In addition, expansion cohort(s) at potential therapeutic dose(s) in patients with or without ESR1 mutations will be enrolled to further determine the safety, tolerability, pharmacokinetics and biological activity of AZD9496
Detailed description
A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD9496 in Women with Estrogen Receptor Positive HER-2 Negative Advanced Breast Cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD9496 | Experimental | Drug: AZD9496AZD9496 dose escalation and expansion(s) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| AZD9496AZD9496 | Drug | AZD9496 |
| AZD9496If initial dosing of AZD9496 is tolerated then subsequent cohorts will test increasing doses until a maximum tolerated dose or maximum feasible dose is defined | Drug | AZD9496 |
Primary outcome
Safety and tolerability
Time frame: Routine safety assessments, throughout the period that patients receive AZD9496 up to 28 days following discontinuation of last dose of study treatment.
Safety and tolerability in terms of adverse events, serious adverse events (including death) and safety measures: ECG, physical examination, vital signs and laboratory variables. Definition of maximum tolerated dose (MTD) or maximum feasible dose (MFD) by measuring the number of evaluable patients with dose-limiting toxicities.Time frame DLT period 28 days
3 secondary outcomes
Single and multiple dose pharmacokinetics of AZD9496
Time frame: 12 weeks
4β-hydroxycholesterol concentration in blood
Time frame: 12 weeks
Antitumour activity
Time frame: every 8 weeks for 24 weeks and then every 12 weeks thereafter until disease progression
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 24 Jun 2019.
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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.
Erika Hamilton principal investigator
Nashville Hospital, United States
Justin Lindemann study director
AstraZeneca
6 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD9496 in people with ER+ HER2- Advanced Breast Cancer, run by AstraZeneca at 6 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 24 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, United Kingdom, South Korea. 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?
Safety and tolerability (time frame: Routine safety assessments, throughout the period that patients receive AZD9496 up to 28 days following discontinuation of last dose of study treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jun 2019.