Breast Neoplasm
Conditions
Keywords
Breast Neoplasm, Breast Cancer, Breast Tumour, Cancer of Breast, Cancer of the Breast
Brief summary
To compare the activity of AZD8931 against placebo on the cell markers in cancer tumours
Detailed description
A Randomised Double-Blind Placebo-controlled Multicentre Phase I Study to Assess the Biological Activity of AZD8931 in Patients with Early Breast Cancer who are Ineligible for Treatment with trastuzumab as defined by IHC status
Interventions
DRUGDrug-AZD8931
Active drug for biological activity
DRUGDrug-Placebo
Placebo comparator for biological activity comparison
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females aged 18 or older Early stage breast cancer and planned surgery * Ineligible for Trastuzumab (Herceptin) treatment as per local guidelines * World health Organisation performance status of 0 to 1 Tumour size amenable to obtaining adequate biopsies pre dosing.
Exclusion criteria
* Eligible for Trastuzumab (Herceptin) Treatment Known sensitivity to AZD8931, its excipients or drugs in its class; * Including oral tyrosine kinase inhibitors History of eye conditions e.g. previous injury within 3 months or clinically significant eye disease * Concurrent malignancy Unable to discontinue medication or herbal supplement known to inhibit CYP3A4 or CYP2D6
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Comparison of the effects of AZD8931 versus placebo on cytoplasmic p-MAPK after 7 days or more days of treatment | Day 7 - Day 14 |
Secondary
| Measure | Time frame |
|---|---|
| Assessment sof the safety and tolerability of AZD8931 as assessed by incidence of adverse events during the course of the study. | From study entry through to 30 days post treatment (Day 44 maximum) |
| Assessment of the plasma PK of AZD8931 | Day 1 - Day 14 |
| Comparison of the effects of AZD8931 versus placebo on other biomarkers including but not limited to, erbB ligands, pER, PTEN, erbB receptor homo- and hetero- dimers, total MAPK, apoptosis markers and total AKT after 7 or more days of treatment. | Day 7 - Day 14 |
| Comparison of the effects of AZD8931 versus placebo on p-EGFR, p-erbB2, p-erbB3 NUCLEAR p-Mapk, p-AKT and Ki67 after 7 or more days of treatment | Day 7 - Day 14 |
| Exploration of the relationship between AZD8931 exposure (PK in plasma and tumour) and a selection of secondary biomarkers (e.g. p-EGFR, nuclear p-MAPK, Ki67 and apoptosis markers after ?7 days of treatment), if possible. | Day 1 - Day 14 |
| Change from baseline in laboratory, vitals signs and ECG data | Day 1 - Day 14 |
| Establishing the baseline tumour characteristics, including but not limited to ER, PR and HER-2 status | Day -28 to Day 0 |
Countries
Germany, South Korea, Taiwan
Outcome results
None listed