Clinical trial NCT01596530: Evaluation of Drug Activity in Women With Breast Cancer and no Previous Herceptin Treatment
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Breast Neoplasm
Keywords: Breast Neoplasm
Breast Cancer
Breast Tumour
Cancer of Breast
Cancer of the Breast
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-05-11
Enrollment: 3
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of the effects of AZD8931 versus placebo on cytoplasmic p-MAPK after 7 days or more days of treatment
timeFrame: Day 7 - Day 14
Secondary outcomes:
measure: 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
timeFrame: Day 7 - Day 14
measure: Assessment sof the safety and tolerability of AZD8931 as assessed by incidence of adverse events during the course of the study.
timeFrame: From study entry through to 30 days post treatment (Day 44 maximum)
measure: Assessment of the plasma PK of AZD8931
timeFrame: Day 1 - Day 14
measure: 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.
timeFrame: Day 7 - Day 14
measure: Establishing the baseline tumour characteristics, including but not limited to ER, PR and HER-2 status
timeFrame: Day -28 to Day 0
measure: 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.
timeFrame: Day 1 - Day 14
measure: Change from baseline in laboratory, vitals signs and ECG data
timeFrame: Day 1 - Day 14
Other outcomes:
Locations:
city: Dusseldorf
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Wittenberg
country: Germany
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Yonsei
country: Korea, Republic of
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
Study officials:
affiliation: Internal
name: Serban Ghiorghiu, M.D.
role: STUDY_DIRECTOR
References: