Investigating safety, tolerability and efficacy of AZD5363 when combined with paclitaxel in breast cancer patients - BEECH

Study identifier:D3610C00002

ClinicalTrials.gov identifier:NCT01625286

EudraCT identifier:2011-006312-31

CTIS identifier:N/A

Study Complete

Official Title

A Phase I/II Study of AZD5363 Combined with Paclitaxel in Patients with Advanced or Metastatic Breast Cancer. Comprising a Safety Run-In and a Placebo-controlled Randomised Expansion in ER+ve Patients Stratified by PIK3CA Mutation Status

Medical condition

advanced or metastatic breast cancer

Phase

Phase 1/2

Healthy volunteers

Study drug

AZD5363 when combined with weekly paclitaxel., AZD5363when combined with weekly paclitaxel., A placebo in combination with weekly paclitaxel.

Sex

Female

Actual Enrollment

148

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 03 Oct 2012

Primary Completion Date: 28 Jan 2017

Study Completion Date: 03 Oct 2022

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Dec 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

This is a Phase I/II multicentre, study investigating the safety, tolerability and efficacy of a twice-daily oral formulation of AZD5363 when combined with a weekly intravenous paclitaxel infusion in patients with advanced or metastatic breast cancer. Study treatment is given in 28-day cycles, comprising three weeks on-therapy followed by one week off-therapy. The study will be conducted in two parts: Part A. Approximately 40 patients will be recruited to this Phase I multiple ascending-dose safety run-in evaluation of each of two intermittent dosing schedules (2 days per week or 4 days per week) of AZD5363 given in combination with weekly paclitaxel. The study population is female patients, 18 years or older, with advanced or metastatic breast cancer. The purpose of Part A is to assess the comparative safety, tolerability, pharmacokinetics and preliminary efficacy of both schedules to determine one dose and schedule of AZD5363 to take forward to study Part B in combination with weekly paclitaxel. Part A assessments will be made in dose-escalating cohorts of 3 to 6 patients to determine a recommended dose in each of the schedules. A total of 6 patients must be evaluated at a selected dose level for it to be confirmed as the recommended dose. All dose evaluations and recommendations will be conducted by a Safety Review Committee. Part A Patients will undergo assessments up to to withdrawal from the study or to discontinuation of study therapy. Part B. A minimum of 100 patients will be recruited to this Phase II double-blind, placebo-controlled, stratified and randomised evaluation of two treatment regimens: AZD5363 (at a dose selected and schedule from Part A) in combination with weekly paclitaxel vs. weekly paclitaxel plus placebo. The study population is female patients with Estrogen Receptor Positive advanced or metastatic breast cancer; of which approximately 50 will have the phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) mutation. Part B patients will be stratified by PIK3CA tumour mutation status as: tumour mutation positive or tumour mutation not-detected. Under each stratum patients will be randomised to receive either paclitaxel + AZD5363 or paclitaxel + placebo. The purpose of Part B is to assess relative efficacy of both active and placebo regimens by comparison of: progression-free survival, overall survival, tumour response, safety and tolerability in the overall ER+ve advanced or metastatic breast cancer population, and in a subgroup of these patients with the PIK3CA tumour mutation. Patient safety and therapy tolerability will be monitored by an independent Safety Review Committee throuighout the course of Part B. Part B patients will be followed for assessment of overall survival, or to withdrawal from the study.

No locations available

Arms	Assigned Interventions
Experimental: Part A: Intermittent schedule (2/5) See intervention description below.	Drug: AZD5363 when combined with weekly paclitaxel. AZD5363: oral capsule, twice daily in a weekly 2 days on-treatment, 5 days-off, schedule. Treatment to begin the day following the first dose of paclitaxel and to continue until treatment withdrawal. Paclitaxel: intravenously once a week. AZD5363 and paclitaxel will be received for 3 consecutive weeks, followed by one week off-therapy in 4-week cycles.
Experimental: Part A: Intermittent schedule (4/3) See intervention description below.	Drug: AZD5363 when combined with weekly paclitaxel. AZD5363: oral capsule, twice daily in a weekly 4 days on-treatment, 3 days-off, schedule. Treatment to begin the day following the first dose of paclitaxel and to continue until treatment withdrawal. Paclitaxel: intravenously once a week. AZD5363 and paclitaxel will be received for 3 consecutive weeks, followed by one week off-therapy in 4-week cycles.
Active Comparator: Part B: AZD5363 combined with paclitaxel See intervention description below.	Drug: AZD5363when combined with weekly paclitaxel. Either a 2/5 or 3/4 intermittent dosing schedule of AZD5363 based on the outcome of Part A. Dosage: oral formulation, twice daily. Treatment to begin the day following the first dose of paclitaxel and to continue until treatment withdrawal. Paclitaxel: intravenously once a week. AZD5363 and paclitaxel will be received for 3 consecutive weeks, followed by one week off-therapy in 4-week cycles.
Placebo Comparator: Part B: paclitaxel combined with placebo See intervention description below.	Drug: A placebo in combination with weekly paclitaxel. Either a 2/5 or 3/4 intermittent dosing schedule of placebo matched to AZD5363 based on the outcome of Part A. Dosage: oral formulation, twice daily. Treatment to begin the day following the first dose of paclitaxel and to continue until treatment withdrawal. Paclitaxel: intravenously once a week. placebo and paclitaxel will be received for 3 consecutive weeks, followed by one week off-therapy in 4-week cycles.

Documents available

CSPandAmendments_redacted
Download
SAP_PartAandB_redactedsignature
Download
SAP_PartAandB_redactedsignature
Download
Redacted CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Justin Lindemann

AstraZeneca