- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02248090
AZD9496 First Time in Patients Ascending Dose Study
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 Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Seoul, Korea, Republic of, 110-744
- Seoul National Univ. Hospital
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Cambridge, United Kingdom, CB2 0QQ
- Research Site
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Manchester, United Kingdom, M20 4BX
- Christie
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Florida
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Sarasota, Florida, United States, 34232
- Florida Cancer Specialists
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New York
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New York, New York, United States, 10065
- Research Site
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Tennessee
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Nashville, Tennessee, United States, 37203
- Sarah Cannon
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: AZD9496
AZD9496 dose escalation and expansion(s)
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AZD9496
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
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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
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Routine safety assessments, throughout the period that patients receive AZD9496 up to 28 days following discontinuation of last dose of study treatment.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Single and multiple dose pharmacokinetics of AZD9496
Time Frame: 12 weeks
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measurement of plasma levels of AZD9496 at pre-defined intervals in order to establish pharmacokinetic parameters
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12 weeks
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4β-hydroxycholesterol concentration in blood
Time Frame: 12 weeks
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Understanding of the CYP3A4 induction potential of AZD9496 by measuring 4β-hydroxycholesterol concentration in blood samples at pre-defined intervals
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12 weeks
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Antitumour activity
Time Frame: every 8 weeks for 24 weeks and then every 12 weeks thereafter until disease progression
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Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
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every 8 weeks for 24 weeks and then every 12 weeks thereafter until disease progression
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Erika Hamilton, Nashville Hospital, United States
- Study Director: Justin Lindemann, AstraZeneca
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- D6090C00001
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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Clinical Trials on AZD9496
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