Evaluation of Drug Activity in Women With Breast Cancer and no Previous Herceptin Treatment

Study Overview
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Brief Summary
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To compare the activity of AZD8931 against placebo on the cell markers in cancer tumours

Detailed Description
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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

Official Title
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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

Conditions
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Breast Neoplasm

Intervention / Treatment
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* Drug: Drug-AZD8931
* Drug: Drug-Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AZD8931<br>AZD8931 | Drug: Drug-AZD8931<br>* Active drug for biological activity<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Drug-Placebo<br>* Placebo comparator for biological activity comparison<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Establishing the baseline tumour characteristics, including but not limited to ER, PR and HER-2 status |  | Day -28 to Day 0 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Neoplasm, Breast Cancer, Breast Tumour, Cancer of Breast, Cancer of the Breast