AZD9496 First Time in Patients Ascending Dose Study

ER+ HER2- Advanced Breast Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02248090
• Other study ID #: D6090C00001
• Status: Completed
• Phase: Phase 1
• Start date: October 22, 2014
• Est. completion date: April 3, 2019

Study information

• Verified date: June 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: April 3, 2019
• Est. primary completion date: January 31, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• ER+ HER2- Advanced Breast Cancer

Intervention

Drug:
• AZD9496
AZD9496
• 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

Locations

Country	Name	City	State
Korea, Republic of	Seoul National Univ. Hospital	Seoul
United Kingdom	Research Site	Cambridge
United Kingdom	Christie	Manchester
United States	Sarah Cannon	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Florida Cancer Specialists	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Routine safety assessments, throughout the period that patients receive AZD9496 up to 28 days following discontinuation of last dose of study treatment.
Secondary	Single and multiple dose pharmacokinetics of AZD9496	measurement of plasma levels of AZD9496 at pre-defined intervals in order to establish pharmacokinetic parameters	12 weeks
Secondary	4ß-hydroxycholesterol concentration in blood	Understanding of the CYP3A4 induction potential of AZD9496 by measuring 4ß-hydroxycholesterol concentration in blood samples at pre-defined intervals	12 weeks
Secondary	Antitumour activity	Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	every 8 weeks for 24 weeks and then every 12 weeks thereafter until disease progression