Advanced or Metastatic Breast CancerPhase 1/2BEECHNCT01625286

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

A Phase 1/2 study testing AZD5363 when combined with weekly paclitaxel. and AZD5363when combined with weekly paclitaxel. in people with Advanced or Metastatic Breast Cancer and ER+ve Advanced or Metastatic Breast Cancer, run by AstraZeneca at 41 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 130 years, women only
Conditions the study is for: Advanced or Metastatic Breast Cancer, ER+ve Advanced or Metastatic Breast Cancer
What is being tested?: AZD5363 when combined with weekly paclitaxel. and AZD5363when combined with weekly paclitaxel.
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 148 participants
Where: 41 sitesin 11 countries
Study dates: 3 Oct 2012to 3 Oct 2022
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 130 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

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, HER2-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.

Who cannot join

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.

Trial locations and contacts

41 sites in 11 countries.

Country

City, postcode or hospital

41 sites in 11 countries

Japan6 sites

Research Site
Chiba, 260-8717
Research Site
Chūōku, 104-0045
Research Site
Fukuoka, 811-1395
Research Site
Mitaka-shi, 181-8611
Research Site
Ōita, 870-0854
Research Site
Osaka, 540-0006

Other trials in Japan

Spain6 sites

Research Site
Barcelona, 08025
Research Site
Madrid, 08035
Research Site
Madrid, 28040
Research Site
Madrid, 28041
Research Site
Málaga, 29010
Research Site
Valencia, 46010

Other trials in Spain

United Kingdom6 sites

Research Site
Glasgow, G12 0YN
Research Site
Leicester, LE1 5WW
Research Site
London, SW3 6JJ
Research Site
Manchester, M20 4BX
Research Site
Plymouth, PL6 8DH.
Research Site
Sutton, SM2 5PT

Other trials in United Kingdom

Canada4 sites

Research Site
Calgary, Alberta, T2N 4N2
Research Site
Montreal, Quebec, H4A 3T2
Research Site
Ottawa, Ontario, K1H 8L6
Research Site
Québec, Quebec, G1S 4L8

Other trials in Canada

Mexico4 sites

Research Site
Estado de México, 50080
Research Site
Juchitán, 7000
Research Site
Monterrey, 64460
Research Site
Oaxaca City, 68000

Other trials in Mexico

Peru4 sites

Research Site
Lima, 15036
Research Site
Lima, L 41
Research Site
Lima, LIMA 27
Research Site
Miraflores, 15046

Other trials in Peru

South Korea4 sites

Research Site
Seongnam-si, 13620
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 135-710

Other trials in South Korea

France3 sites

Research Site
Paris, 75248
Research Site
Pierre-Bénite, 69310
Research Site
Villejuif, 94805

Other trials in France

Bulgaria2 sites

Research Site
Plovdiv, 4004
Research Site
Sofia, 1330

Other trials in Bulgaria

Czechia1 site

Research Site
Brno, 656 53

Other trials in Czechia

Singapore1 site

Research Site
Singapore, 119228

Other trials in Singapore

About this study

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

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.

Read the detailed description

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.

Conditions: Advanced or Metastatic Breast Cancer, ER+ve Advanced or Metastatic Breast Cancer
Being tested: AZD5363 when combined with weekly paclitaxel., AZD5363when combined with weekly paclitaxel., A placebo in combination with weekly paclitaxel.
Keywords: advanced breast cancer,, metastatic breast cancer,, ER+ve breast cancer,, Estrogen receptor positive breast cancer,, PIK3CA mutated advanced or metastatic breast cancer, AKT inhibitor
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01625286
Study group	Role	What they receive
Part A: Intermittent schedule (2/5)	Experimental	See intervention description below. Receives: Drug: AZD5363 when combined with weekly paclitaxel.
Part A: Intermittent schedule (4/3)	Experimental	See intervention description below. Receives: Drug: AZD5363 when combined with weekly paclitaxel.
Part B: AZD5363 combined with paclitaxel	Active comparator	See intervention description below. Receives: Drug: AZD5363when combined with weekly paclitaxel.
Part B: paclitaxel combined with placebo	Placebo comparator	See intervention description below. Receives: Drug: A placebo in combination with weekly paclitaxel.

What is being measured

The primary outcome is the main question the study is designed to answer.

Dose-limiting Toxicity (DLT) Events - Part A
An Adverse Event (AE) or laboratory abnormality considered to be related to study drug, that starts at any time during the DLT evaluation period (Cycle 1) and is dose limiting
Measured: During Part A DLT evaluation period (Cycle 1, up to 28 days)
Progression Free Survival (PFS) - Part B
Time from randomisation to date of objective disease progression or death (by any cause in the absence of progression). Progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a >= 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, and an absolute increase of >=5mm, or progression of non-target lesions or the appearance of new lesions.
Measured: From randomisation date to date of objective disease progression or death (by any cause) whichever came first, assessed every 12 wks (median total treatment duration AZD5363=325.5 days; Placebo=245 days)

Secondary outcomes (8)

Change in Tumour Size at 12 Weeks
Percentage change from baseline to week 12 in sum of longest diameters of target lesions as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1). Based on patients with measurable disease who had sufficient data available to either calculate or impute a change at 12 weeks
Measured: RECIST tumour assessments every 12 weeks
Objective Response Rate (ORR) at Week 12
Percentage of patients who have at least one visit response of Complete Response or Partial Response prior to any evidence of progression at week 12 as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR
Measured: RECIST tumour assessments every 12 weeks
Best Objective Response (BOR)
Number of patients, taking their BOR, which is their best objective tumour response based on RECIST measurements throughout the whole study as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm.
Measured: From date of randomisation, assessed every 12 weeks (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).
Overall Objective Response Rate
Percentage of patients, taking their best objective tumour response based on RECIST measurements throughout the whole study as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm. Overall Response Rate (ORR) = CR + PR
Measured: From date of randomisation, assessed every 12 weeks (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).
Number of Subjects Without Progression Disease at Week 12 - Part A
Percentage of patients with a 12 week visit response of CR, PR or SD (as defined by RECIST 1.1) with no evidence of previous progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm.
Measured: up to 12 weeks
Duration of Response (DOR) - Part B
Date of first documentation of response (Complete Response/Partial Response) until the date of disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm.. If a subject does not progress following a response, then their DOR will use the PFS censoring time.
Measured: From date of randomisation, assessed every 12 weeks (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).
Durable Response Rate (DRR) - Part B
Percentage of patients who have a Complete Response (CR) or Partial Response (PR) lasting continuously for at least 24 weeks as defined by Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: PR, >=30% decrease in the sum of the longest diameter of target lesions; CR, disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm.
Measured: From date of randomisation, assessed every 12 weeks (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).
Overall Survival - Part B
The interval between the date of randomisation and the date of patient death due to any cause. All Part B patients were analysed, number of deaths is presented.
Measured: From date of randomisation, assessed every 12 weeks, up until the time of final statistical analysis. (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Oct 20123 Oct 2022

First posted21 Jun 2012 (estimated)
Study start3 Oct 2012
Primary completion28 Jan 2017
Study completion3 Oct 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Advanced or Metastatic Breast CancerStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 148 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01625286
Sponsor's protocol ID: D3610C00002
Other IDs: 2011-006312-31
Acronym: BEECH
Status last verified: Dec 2022
First submitted: 10 May 2012
Last updated: 18 Jan 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

Publications

Hrebien S, Citi V, Garcia-Murillas I, Cutts R, Fenwick K, Kozarewa I, McEwen R, Ratnayake J, Maudsley R, Carr TH, de Bruin EC, Schiavon G, Oliveira M, Turner N. Early ctDNA dynamics as a surrogate for progression-free survival in advanced breast cancer in the BEECH trial. Ann Oncol. 2019 Jun 1;30(6):945-952. doi: 10.1093/annonc/mdz085.
PubMed 30860573
Turner NC, Alarcon E, Armstrong AC, Philco M, Lopez Chuken YA, Sablin MP, Tamura K, Gomez Villanueva A, Perez-Fidalgo JA, Cheung SYA, Corcoran C, Cullberg M, Davies BR, de Bruin EC, Foxley A, Lindemann JPO, Maudsley R, Moschetta M, Outhwaite E, Pass M, Rugman P, Schiavon G, Oliveira M. BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Ann Oncol. 2019 May 1;30(5):774-780. doi: 10.1093/annonc/mdz086.
PubMed 30860570

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 18 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01625286
Acronym / sponsor ID: BEECH / D3610C00002
Conditions: Advanced or Metastatic Breast Cancer, ER+ve Advanced or Metastatic Breast Cancer
Keywords: advanced breast cancer,, metastatic breast cancer,, ER+ve breast cancer,, Estrogen receptor positive breast cancer,, PIK3CA mutated advanced or metastatic breast cancer, AKT inhibitor
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 148 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 3 Oct 2012 (actual)
Primary completion: 28 Jan 2017 (actual)
Study completion: 3 Oct 2022 (actual)
First posted: 21 Jun 2012 (estimated)
Results: Posted 1 Apr 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The study will be conducted in two parts:

Part A Patients will undergo assessments up to to withdrawal from the study or to discontinuation of study therapy.

Part B patients will be followed for assessment of overall survival, or to withdrawal from the study.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Part A: Intermittent schedule (2/5)	Experimental	Drug: AZD5363 when combined with weekly paclitaxel.See intervention description below.
Part A: Intermittent schedule (4/3)	Experimental	Drug: AZD5363 when combined with weekly paclitaxel.See intervention description below.
Part B: AZD5363 combined with paclitaxel	Active comparator	Drug: AZD5363when combined with weekly paclitaxel.See intervention description below.
Part B: paclitaxel combined with placebo	Placebo comparator	Drug: A placebo in combination with weekly paclitaxel.See intervention description below.

Who may qualify

Ages: 18 to 130 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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, HER2-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.

Key exclusion criteria (6 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
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	Part A: Intermittent schedule (2/5)
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	Part A: Intermittent schedule (4/3)
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	Part B: AZD5363 combined with paclitaxel
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.	Drug	Part B: paclitaxel combined with placebo

Primary outcome

Dose-limiting Toxicity (DLT) Events - Part A
Time frame: During Part A DLT evaluation period (Cycle 1, up to 28 days)
An Adverse Event (AE) or laboratory abnormality considered to be related to study drug, that starts at any time during the DLT evaluation period (Cycle 1) and is dose limiting
Progression Free Survival (PFS) - Part B
Time frame: From randomisation date to date of objective disease progression or death (by any cause) whichever came first, assessed every 12 wks (median total treatment duration AZD5363=325.5 days; Placebo=245 days)
Time from randomisation to date of objective disease progression or death (by any cause in the absence of progression). Progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a >= 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on the study, and an absolute increase of >=5mm, or progression of non-target lesions or the appearance of new lesions.

8 secondary outcomes

Change in Tumour Size at 12 Weeks
Time frame: RECIST tumour assessments every 12 weeks
Objective Response Rate (ORR) at Week 12
Time frame: RECIST tumour assessments every 12 weeks
Best Objective Response (BOR)
Time frame: From date of randomisation, assessed every 12 weeks (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).
Overall Objective Response Rate
Time frame: From date of randomisation, assessed every 12 weeks (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).
Number of Subjects Without Progression Disease at Week 12 - Part A
Time frame: up to 12 weeks
Duration of Response (DOR) - Part B
Time frame: From date of randomisation, assessed every 12 weeks (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).
Durable Response Rate (DRR) - Part B
Time frame: From date of randomisation, assessed every 12 weeks (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).
Overall Survival - Part B
Time frame: From date of randomisation, assessed every 12 weeks, up until the time of final statistical analysis. (median total treatment duration AZD5363 = 325.5 days; Placebo = 245 days).

Results and safety

Results posted to the registry on 1 Apr 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A Schedule 1 560 mg bd	12	6
Part A Schedule 1 640 mg bd	8	4
Part A Schedule 2 360 mg bd	5	0
Part A Schedule 2 400 mg bd	7	0
Part A Schedule 2 480 mg bd	6	0
Part B AZD5363	54	40
Part B Placebo	56	37

Primary outcome: Dose-limiting Toxicity (DLT) Events - Part A

Time frame: During Part A DLT evaluation period (Cycle 1, up to 28 days). Number. Unit: participants

Measure	Part A Schedule 1 560 mg bd n = 11	Part A Schedule 1 640 mg bd n = 6	Part A Schedule 2 360 mg bd n = 5	Part A Schedule 2 400 mg bd n = 7	Part A Schedule 2 480 mg bd n = 6	Part B AZD5363 n = 0	Part B Placebo n = 0
Value	0	2	0	0	2	–	–

Population analysed: All Part A patients who either completed the DLT evaluation period with at least 80% of specified dose (of AZD5363 or paxlitaxel) or who experienced a DLT. DLT events were not assessed for Part B participants.

Primary outcome: Progression Free Survival (PFS) - Part B

Time frame: From randomisation date to date of objective disease progression or death (by any cause) whichever came first, assessed every 12 wks (median total treatment duration AZD5363=325.5 days; Placebo=245 days). Median (95% Confidence Interval). Unit: Months

Measure	Part A Schedule 1 560 mg bd n = 0	Part A Schedule 1 640 mg bd n = 0	Part A Schedule 2 360 mg bd n = 0	Part A Schedule 2 400 mg bd n = 0	Part A Schedule 2 480 mg bd n = 0	Part B AZD5363 n = 54	Part B Placebo n = 56
Value	–	–	–	–	–	10.9 (8.3 to 12.4)	8.4 (8.2 to 10.8)

Part B AZD5363 vs Part B Placebo: Hazard Ratio (HR): 0.80 (80% CI 0.60 to 1.06), p = 0.308, Regression, Cox

Population analysed: Intent to Treat (ITT), all randomised patients

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: Time of signature of informed consent throughout the treatment period up to and including the follow-up period (median follow-up AZD5363 16.9 months; Placebo 15.2 months). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A Schedule 1 560 mg bd	3 of 12 (25%)	12 of 12 (100%)	0 of 12
Sched 1 - AZD5363 640 mg bd	3 of 8 (37.5%)	8 of 8 (100%)	0 of 8
Sched 2 - AZD5363 360 mg bd	0 of 5 (0%)	5 of 5 (100%)	1 of 5
Sched 2 - AZD5363 400 mg bd	1 of 7 (14.3%)	7 of 7 (100%)	1 of 7
Part A Schedule 2 480 mg bd	4 of 6 (66.7%)	6 of 6 (100%)	0 of 6
Part B AZD5363	13 of 54 (24.1%)	50 of 54 (92.6%)	13 of 54
Part B Placebo	8 of 55 (14.5%)	48 of 55 (87.3%)	15 of 56

Limitations and caveats (from the sponsor): QoL, PK/PD \& efficacy response modelling were considered non-key secondary endpoints and not disclosed at this time. QoL data was limited and considered exploratory, PK/PD and modelling were not reported in CSR. Diarrhoea burden is reported with AEs

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30860573Hrebien S, Citi V, Garcia-Murillas I, Cutts R, Fenwick K, Kozarewa I, McEwen R, Ratnayake J, Maudsley R, Carr TH, de Bruin EC, Schiavon G, Oliveira M, Turner N. Early ctDNA dynamics as a surrogate for progression-free survival in advanced breast cancer in the BEECH trial. Ann Oncol. 2019 Jun 1;30(6):945-952. doi: 10.1093/annonc/mdz085.
Derived from this study: PubMed 30860570Turner NC, Alarcon E, Armstrong AC, Philco M, Lopez Chuken YA, Sablin MP, Tamura K, Gomez Villanueva A, Perez-Fidalgo JA, Cheung SYA, Corcoran C, Cullberg M, Davies BR, de Bruin EC, Foxley A, Lindemann JPO, Maudsley R, Moschetta M, Outhwaite E, Pass M, Rugman P, Schiavon G, Oliveira M. BEECH: a dose-finding run-in followed by a randomised phase II study assessing the efficacy of AKT inhibitor capivasertib (AZD5363) combined with paclitaxel in patients with estrogen receptor-positive advanced or metastatic breast cancer, and in a PIK3CA mutant sub-population. Ann Oncol. 2019 May 1;30(5):774-780. doi: 10.1093/annonc/mdz086.
CSPandAmendments\_redactedLink provided by the sponsor.
SAP\_PartAandB\_redactedsignatureLink provided by the sponsor.
SAP\_PartAandB\_redactedsignatureLink provided by the sponsor.
Redacted CSR SynopsisLink provided by the sponsor.
Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Justin Lindemann, MBChB MBA study director

AstraZeneca

41 sites in 11 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in Japan, Spain, United Kingdom, Canada, Mexico and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting Toxicity (DLT) Events - Part A (time frame: During Part A DLT evaluation period (Cycle 1, up to 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01625286, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2023.