AZD9496 First Time in Patients Ascending Dose Study

Phase 1

Completed

• Conditions: ER+ HER2- Advanced Breast Cancer
• Interventions: Drug: AZD9496

• Registration Number: NCT02248090
• Lead Sponsor: AstraZeneca

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

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 Timeline

• Study First Submitted: 2014-09-22
• Study First Submitted QC: 2014-09-22
• Study First Posted: 2014-09-25
• Study Start: 2014-10-22
• Primary Completion: 2017-01-31
• Study Completion: 2019-04-03
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-21
• Last Update Posted: 2019-06-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 45

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AZD9496	AZD9496	AZD9496 dose escalation and expansion(s)

Primary Outcome Measures

Name	Time	Method
Safety and tolerability	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

Name	Time	Method
4β-hydroxycholesterol concentration in blood	12 weeks	Understanding of the CYP3A4 induction potential of AZD9496 by measuring 4β-hydroxycholesterol concentration in blood samples at pre-defined intervals
Single and multiple dose pharmacokinetics of AZD9496	12 weeks	measurement of plasma levels of AZD9496 at pre-defined intervals in order to establish pharmacokinetic parameters
Antitumour activity	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)

Trial Locations

Locations (5)

Florida Cancer Specialists; 🇺🇸 Sarasota, Florida, United States

Sarah Cannon; 🇺🇸 Nashville, Tennessee, United States

Research Site; 🇬🇧 Cambridge, United Kingdom

Seoul National Univ. Hospital; 🇰🇷 Seoul, Korea, Republic of

Christie; 🇬🇧 Manchester, United Kingdom