Clinical Trials /

AZD9496 First Time in Patients Ascending Dose Study

NCT02248090

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: AZD9496 First Time in Patients Ascending Dose 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

Clinical Trial IDs

  • ORG STUDY ID: D6090C00001
  • NCT ID: NCT02248090

Conditions

  • ER+ HER2- Advanced Breast Cancer

Interventions

DrugSynonymsArms
AZD9496AZD9496
AZD9496AZD9496

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
AZD9496ExperimentalAZD9496 dose escalation and expansion(s)
  • AZD9496
  • AZD9496

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

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.
Safety Issue:
Description: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

Measure:Single and multiple dose pharmacokinetics of AZD9496
Time Frame:12 weeks
Safety Issue:
Description:measurement of plasma levels of AZD9496 at pre-defined intervals in order to establish pharmacokinetic parameters
Measure:4β-hydroxycholesterol concentration in blood
Time Frame:12 weeks
Safety Issue:
Description:Understanding of the CYP3A4 induction potential of AZD9496 by measuring 4β-hydroxycholesterol concentration in blood samples at pre-defined intervals
Measure:Antitumour activity
Time Frame:every 8 weeks for 24 weeks and then every 12 weeks thereafter until disease progression
Safety Issue:
Description:Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • Phase 1
  • Safety
  • Tolerability
  • Pharmacokinetics
  • Ascending Doses
  • Estrogen Receptor Positive
  • Her2 Negative
  • Advanced Breast Cancer

Last Updated

November 22, 2017