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AZD9496 First Time in Patients Ascending Dose Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02248090
Recruitment Status : Completed
First Posted : September 25, 2014
Last Update Posted : June 24, 2019
Information provided by (Responsible Party):

Brief 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. 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

Condition or disease Intervention/treatment Phase
ER+ HER2- Advanced Breast Cancer Drug: AZD9496 Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 22, 2014
Actual Primary Completion Date : January 31, 2017
Actual Study Completion Date : April 3, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: AZD9496
AZD9496 dose escalation and expansion(s)
Drug: AZD9496

Drug: 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

Primary Outcome Measures :
  1. 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

Secondary Outcome Measures :
  1. Single and multiple dose pharmacokinetics of AZD9496 [ Time Frame: 12 weeks ]
    measurement of plasma levels of AZD9496 at pre-defined intervals in order to establish pharmacokinetic parameters

  2. 4β-hydroxycholesterol concentration in blood [ Time Frame: 12 weeks ]
    Understanding of the CYP3A4 induction potential of AZD9496 by measuring 4β-hydroxycholesterol concentration in blood samples at pre-defined intervals

  3. Antitumour activity [ Time Frame: every 8 weeks for 24 weeks and then every 12 weeks thereafter until disease progression ]
    Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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

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 identifier (NCT number): NCT02248090

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United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, New York
Research Site
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon
Nashville, Tennessee, United States, 37203
Korea, Republic of
Seoul National Univ. Hospital
Seoul, Korea, Republic of, 110-744
United Kingdom
Research Site
Cambridge, United Kingdom, CB2 0QQ
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
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Principal Investigator: Erika Hamilton Nashville Hospital, United States
Study Director: Justin Lindemann AstraZeneca
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Responsible Party: AstraZeneca Identifier: NCT02248090    
Other Study ID Numbers: D6090C00001
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: June 24, 2019
Last Verified: June 2019
Keywords provided by AstraZeneca:
Phase 1
Ascending Doses
Estrogen Receptor Positive
Her2 Negative
Advanced Breast Cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases