Investigating Safety, Tolerability and Efficacy of AZD5363 When Combined With Paclitaxel in Breast Cancer Patients (BEECH)

This study is currently recruiting participants.
Verified April 2014 by AstraZeneca
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01625286
First received: May 10, 2012
Last updated: April 14, 2014
Last verified: April 2014

May 10, 2012
April 14, 2014
October 2012
April 2016   (final data collection date for primary outcome measure)
  • Part A: Safety and tolerability of AZD5363 when combined with paclitaxel, in terms of numbers of patients with adverse events and serious adverse events. [ Time Frame: Adverse events and toxicities recorded from patient screening to first of: date of withdrawal from study, date of death or date of patient completion of study. Average participation approximately 18 weeks. ] [ Designated as safety issue: Yes ]
  • Part B: Relative efficacy of AZD5363, compared to placebo, when combined with paclitaxel, by assessment of progression-free survival. [ Time Frame: Tumour assessments by RECIST at screening and at 12 weekly intervals until first of: date of first documented progression, date of study withdrawal or date of death. Average participation approximately 18 weeks. ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01625286 on ClinicalTrials.gov Archive Site
  • Part A: Preliminary anti-tumour activity of AZD5363 when combined with paclitaxel, by assessment of overall response rate (ORR) and percentage of patients without progressive disease at 12 weeks. [ Time Frame: Tumour assessment by RECIST at patient screening and at 12 weeks after date of start of study therapy. ] [ Designated as safety issue: No ]
  • Part B: Relative efficacy of AZD5363, compared to placebo, when combined with paclitaxel, by assessment of ORR at 12 weeks, best objective response (BOR) and duration of response (DoR). [ Time Frame: Tumour assessment by RECIST at patient screening and at 12 weeks after date of start of study therapy (ORR) and first of: date of first documented progression, date of study withdrawal or date of death. Average participation approximately 18 weeks. ] [ Designated as safety issue: No ]
  • Part B: Relative anti-tumour activity of AZD5363, compared to placebo, when combined with paclitaxel, by comparison of change in tumouir size at 12 weeks. [ Time Frame: Tumour assessment by RECIST at screening and at 12 weeks after date of start of study therapy. ] [ Designated as safety issue: No ]
  • Part B: Safety and tolerability of AZD5363 when combined with paclitaxel,in terms of numbers of patients with adverse events and serious adverse events. [ Time Frame: Adverse events and toxicities recorded from patient screening to first of: date of study withdrawal, date of death or 28 days after date of discontinuation of all study therapies. Average participation approximately 24 weeks. ] [ Designated as safety issue: Yes ]
  • Part B: Effect on patient's quality of life (QoL) due to receipt of AZD5363 when combined with paclitaxel, by assessing changes from baseline score in a patient-completed QoL questionnaire (EORTC QLQ-30 / BR-23). [ Time Frame: QoL questionnaires completed at screening and at 12 weekly intervals from screening until first of: date of study withdrawal, date of death or date of discontinuation of all study therapies. Average participation approximately 24 weeks. ] [ Designated as safety issue: No ]
  • Parts A and B: Assessment of the plasma concentration profile of AZD5363 when combined with paclitaxel. [ Time Frame: AZD5363 plasma concentration samples will be collected during the first treatment cycle on: days 2, 3, 5, 9, 16 and 2 from date of start of study therapy. ] [ Designated as safety issue: No ]
  • Parts A and B: Assessment of the plasma concentration (PK) profile of paclitaxel alone and when combined with AZD5363. [ Time Frame: Paclitaxel plasma concentration samples will be collected during the first treatment cycle on: days 1, 2, 9, and 16 from date of start of study therapy. ] [ Designated as safety issue: No ]
  • Parts A and B: Assessment of the pharmacokinetic/pharmacodynamic relationship between plasma concentration of AZD5363 and plasma concentrations of pharmacodynamic biomarkers and correlation with anti-tumour activity. [ Time Frame: PPD samples will be collected on days 1, 2, 3, 5, 9, 16 and 23 from therapy start, then day 1 of each cycle. AZD5363 PK sampling and anti-tumour activity assessment timepoints are as decribed previously. Average participation approximately 18 weeks. ] [ Designated as safety issue: No ]
  • Part B: Overall survival of patients treated with AZD5363, compared to placebo, when in combination with paclitaxel by assessment of time to death. [ Time Frame: First of: date of study withdrawal or date of death. Average participation approximately 52 weeks. ] [ Designated as safety issue: No ]
  • Part A: Preliminary anti-tumour activity of AZD5363 when combined with paclitaxel, by assessment of overall response rate (ORR) and percentage of patients without progressive disease at 12 weeks. [ Time Frame: Tumour assessment by RECIST at patient screening and at 12 weeks after date of start of study therapy. ] [ Designated as safety issue: No ]
  • Part B: Relative efficacy of AZD5363, compared to placebo, when combined with paclitaxel, by assessment of ORR at 12 weeks. [ Time Frame: Tumour assessment by RECIST at patient screening and at 12 weeks after date of start of study therapy ] [ Designated as safety issue: No ]
  • Part B: Relative efficacy of AZD5363, compared to placebo, when combined with paclitaxel, by assessment of: progression-free survival time (PFS), best objective response (BOR) and duration of response (DoR) [ Time Frame: Tumour assessment by RECIST at screening and at 12 weekly intervals from date of start of study therapy until first of: date of first documented progression, date of study withdrawal or date of death. Average participation approximately 18 weeks. ] [ Designated as safety issue: No ]
  • Part B: Safety and tolerability of AZD5363 when combined with paclitaxel,in terms of numbers of patients with adverse events and serious adverse events. [ Time Frame: Adverse events and toxicities recorded from patient screening to first of: date of study withdrawal, date of death or 28 days after date of discontinuation of all study therapies. Average participation approximately 24 weeks. ] [ Designated as safety issue: Yes ]
  • Part B: Effect on patient's quality of life (QoL) due to receipt of AZD5363 when combined with paclitaxel, by assessing changes from baseline score in a patient-completed QoL questionnaire (EORTC QLQ-30 / BR-23). [ Time Frame: QoL questionnaires completed at screening and at 12 weekly intervals from screening until first of: date of study withdrawal, date of death or date of discontinuation of all study therapies. Average participation approximately 24 weeks. ] [ Designated as safety issue: No ]
  • Parts A and B: Assessment of the plasma concentration profile of AZD5363 when combined with paclitaxel. [ Time Frame: AZD5363 plasma concentration samples will be collected during the first treatment cycle on: days 2, 3, 8, 9, 16 and 23 (continuous dosing schedule) or days 2, 3, 5, 9, 16 and 23 (intermittent dosing schedule) from date of start of study therapy. ] [ Designated as safety issue: No ]
  • Parts A and B: Assessment of the plasma concentration (PK) profile of paclitaxel alone and when combined with AZD5363. [ Time Frame: Paclitaxel plasma concentration samples will be collected during the first treatment cycle on: days 1, 2, 8, 9 and 15 (continuous dosing schedule) or days 1, 2, 9, and 16 (intermittent dosing schedule) from date of start of study therapy. ] [ Designated as safety issue: No ]
  • Parts A and B: Assessment of the relationship between plasma concentration of AZD5363 with plasma concentrations of pharmacodynamic (PD) biomarkers and correlation with anti-tumour activity. [ Time Frame: PD samples will be collected on: days 1, 2, 3, 8, 9, 15 and 22 (continuous schedule) or 1, 2, 3, 5, 9, 16 and 23 (intermittent schedule) from therapy start. AZD5363 PK samples will be collected and 12-weekly RECIST assessed as described above. ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Investigating Safety, Tolerability and Efficacy of AZD5363 When Combined With Paclitaxel in Breast Cancer Patients
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.

The purpose of this study is to investigate the safety and efficacy of different doses and schedules of AZD5363, when in combination with paclitaxel, in treatment of patients with advanced or metastatic breast cancer. Also to investigate a selected dose and schedule of AZD5363 in combination with paclitaxel vs. paclitaxel in combination with placebo in treatment of patients with estrogen receptor-positive advanced or metastatic breast cancer, including a subgroup who have the phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) tumour mutation.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Advanced or Metastatic Breast Cancer,
  • ER+ve Advanced or Metastatic Breast Cancer.
  • 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.
  • 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.
  • 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.
  • 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.
  • Experimental: Part A: Intermittent schedule (2/5)
    See intervention description below.
    Intervention: Drug: AZD5363 when combined with weekly paclitaxel.
  • Experimental: Part A: Intermittent schedule (4/3)
    See intervention description below.
    Intervention: Drug: AZD5363 when combined with weekly paclitaxel.
  • Active Comparator: Part B: AZD5363 combined with paclitaxel
    See intervention description below.
    Intervention: Drug: AZD5363when combined with weekly paclitaxel.
  • Placebo Comparator: Part B: paclitaxel combined with placebo
    See intervention description below.
    Intervention: Drug: A placebo in combination with weekly paclitaxel.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
October 2016
April 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Provision of informed consent.
  • Female patient.
  • Aged at least 18 years.
  • Histological or cytological confirmation of breast cancer with evidence of advanced or metastatic disease (must be ER+ve in Part B).
  • World Health Organisation (WHO) performance status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks.

Exclusion Criteria:

  • Clinically significant abnormalities of glucose metabolism.
  • Spinal cord compression or brain metastases unless asymptomatic, treated and stable (not requiring steroids).
  • Evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses or active infections including hepatitis B, C and HIV.
  • Any prior exposure to agents which inhibit AKT as the primary pharmacological activity.
  • Part A: more than two prior courses of chemotherapy (including taxanes) for advanced or metastatic breast cancer.

Part B: any prior chemotherapy for advanced or metastatic breast cancer.

Female
18 Years and older
No
Contact: AstraZeneca Clinical Study Information 800-236-9933 ClinicalTrialTransparency@astrazeneca.com
Bulgaria,   France,   Japan,   Mexico,   Netherlands,   Peru,   Spain,   United Kingdom
 
NCT01625286
D3610C00002
No
AstraZeneca
AstraZeneca
Not Provided
Study Director: Justin Lindemann, MBChB MBA AstraZeneca
AstraZeneca
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP