AKT Inhibitor in Oestrogen Positive Breast Cancer

NCT02077569 | Completed Phase 2 DMC

• 1 other identifier: 12076
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 11

Brief Summary

To compare the effect of four and a half days treatment of a range of doses of AZD5363 on selected markers of the AKT pathway and anti-proliferation compared with placebo in oestrogen receptor positive breast cancers. To assess the tolerability of four and a half days treatment of AZD5363.

Conditions

Invasive Breast Cancer

Keywords

AKT inhibitor; AZD5363; Anti-tumour activity; Breast cancer; ER positive; Oestrogen positive; post menopausal; chemotherapy required; no prior cancer treatment

Outcome Measures

Primary Outcomes (1)

• Primary endpoint: Pharmacodynamic biomarker analysis in tumour tissue to assess the biological effect of AZD5363 on markers of anti-proliferation and the AKT pathway

  Changes in pPRAS40, pGSK3b, Ki67

  Up to 42 months: Stage 1: up to 60 participants in up to 20 months. Stage 1 biomarker analysis early in Stage 2. Stage 2 proceeds where reduction in 1 of the 3 primary biomarkers. Stage 2: up to 60 participants in up to 16 months.

Secondary Outcomes (3)

• Compare anti-proliferative effect on markers of the AKT pathway after 4&1/2days treatment at 3 different doses of AZD5363 vs placebo in Er +ve breast cancers

  Up to 42 months. Stage 1: up to 60 participants in up to 20 months. Stage 2: up to 60 participants in up to 16 months.

• Compare direct effect on markers of the AKT pathway after 4&1/2days treatment at 3 different doses of AZD5363 vs placebo in Er +ve breast cancers

  Up to 42 months. Stage 1: up to 60 participants in up to 20 months. Stage 2: up to 60 participants in up to 16 months.

• To measure tolerability and toxicity following short term (four and a half days) exposure to AZD5363

  Up to 42 months. Stage 1: up to 60 participants in up to 20 months. Stage 2: up to 60 participants in up to 16 months.

Study Arms (4)

AZD5363 480mg

EXPERIMENTAL

STAGE 1 ONLY AZD5363 480mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule

Drug: AZD5363

Placebo

PLACEBO COMPARATOR

STAGE 1 ONLY Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule

Drug: AZD5363

AZD360mg

EXPERIMENTAL

STAGE 2 AZD5363 360mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule

Drug: AZD5363

AZD5363 240mg

EXPERIMENTAL

STAGE 2 AZD5363 240mg Twice daily dosing for 4 and 1/2 days (9 doses) Oral Capsule

Drug: AZD5363

Interventions

AZD5363 DRUG

Stage 1: AZD5363 480mg or placebo twice daily oral dosing for 4 and 1/2 days (9 doses) Stage 2: AZD5363 360mg or 240mg daily oral dosing for 4 and 1/2 days (9 doses)

AZD360mg; AZD5363 240mg; AZD5363 480mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• WHO performance status 0-1.
• Able to swallow \& retain oral medication.
• Patients who fall in to either category (a) or (b):
• Post-menopausal patients
• Pre-menopausal patients who also meet at least one of the criteria (i), (ii) or (iii) below:
• i) hysterectomy or bilateral fallopian tube ligation at least 6 weeks ago plus a negative pregnancy test.
• ii) true abstinence iii) willing to have pregnancy testing and use 2 forms of contraception
• Female patients, aged 18 years and over, with histological confirmation of ER positive invasive breast carcinoma.
• Stage 1/2/3 or Stage 4 with primary tumour in the breast amenable to biopsies. New primary breast tumours (ipsi- or contra-lateral) despite prior endocrine treatment for an earlier primary breast tumour with at least 12 months interval between cessation of endocrine therapy and Visit 1 are eligible.
• Scheduled to have chemotherapy based on tumour characteristics and local treatment protocols.
• Tumours large enough to provide sufficient tissue to be taken by core-cut or tru-cut biopsy to provide tissue sections for the marker assays.

You may not qualify if:

• Known ER negative tumour.
• Female patients with histological confirmation of ER+ve invasive breast carcinoma not scheduled to have chemotherapy
• Exposure to potent inhibitors or inducers of CYP3A4 or CYP2D6 or substrates of CYP3A4 within 2 weeks before the first dose of study treatment (3 weeks for St Johns Wort).
• Clinically significant abnormalities of glucose metabolism
• Major surgery (excluding placement of vascular access) within 4 weeks before the first dose of study treatment.
• Spinal cord compression or brain metastases.
• Evidence of severe or uncontrolled systemic disease.
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc)\>450 msec obtained from 3 consecutive ECGs; - Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events.
• Any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure NYHA Grade 2.
• Uncontrolled hypotension.
• Absolute neutrophil count \<1.5 x 10,000,000,000/L
• Platelet count \<100 x 10,000,000,000/L.
• Haemoglobin \<90 g/L

Sponsors & Collaborators

• University of Nottingham: lead
• AstraZeneca: collaborator
• Cancer Research UK: collaborator
• National Cancer Research Network: collaborator

Study Sites (11)

Royal Derby Hospital

Derby, Derbyshire, DE22 3DT, United Kingdom

Location

Plymouth Hospitals NHS Trust

Derriford, Plymouth, Devon, PL6 8DH, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, Dorset, BH7 7DW, United Kingdom

Location

Poole Hospital NHS Foundation Trust

Poole, Dorset, BH15 2JB, United Kingdom

Location

Leicester Royal Infirmary

Leicester, Leicestershire, LE1 5WW, United Kingdom

Location

Western General Hospital

Edinburgh, Lothian, EH4 2XU, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

Kingsmill Hospital

Sutton in Ashfield, Nottinghamshire, NG17 4JL, United Kingdom

Location

Sheffield Cancer Research Centre

Sheffield, South Yorkshire, S10 2SJ, United Kingdom

Location

University Hospital Birmingahm

Birmingham, West Midlands, B15 2TT, United Kingdom

Location

Leeds St James Institue of Oncology

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

capivasertib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• John FR Robertson, MD

  University of Nottingham

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2014
• First Posted: March 4, 2014
• Study Start: January 1, 2014
• Primary Completion: February 21, 2017
• Study Completion: February 21, 2017
• Last Updated: May 4, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (11)