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

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

To compare the activity of AZD8931 against placebo on the cell markers in cancer tumours

Study Overview

• Status: Terminated
• Conditions: Breast Neoplasm
• Intervention / Treatment: Drug: Drug-AZD8931; Drug: Drug-Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Dusseldorf, Germany
    • Research Site
  • Essen, Germany
    • Research Site
  • Wittenberg, Germany
    • Research Site
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Research Site
  • Yonsei, Korea, Republic of
    • Research Site
• Taiwan
  • Taichung, Taiwan
    • Research Site
  • Taipei, Taiwan
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Drug-Placebo; Placebo comparator for biological activity comparison
ACTIVE_COMPARATOR: AZD8931	Drug: Drug-AZD8931; Active drug for biological activity

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Serban Ghiorghiu, M.D., Internal

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ANTICIPATED): March 1, 2013
• Study Completion (ANTICIPATED): May 1, 2013

Study Registration Dates

• First Submitted: April 27, 2012
• First Submitted That Met QC Criteria: May 9, 2012
• First Posted (ESTIMATE): May 11, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 17, 2012
• Last Update Submitted That Met QC Criteria: December 13, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: Breast Cancer; Cancer of the Breast; Breast Neoplasm; Cancer of Breast; Breast Tumour
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: D0102C00019