Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Contact information



Primary contact

Mrs Gemma Earl


Contact details

Clinical Investigation and Research Unit
Royal Sussex County Hospital
Eastern Road
United Kingdom

Additional identifiers

EudraCT number

2011-003530-13 number

Protocol/serial number


Study information

Scientific title



Study hypothesis

This open-label, randomised phase II study of 2-week preoperative treatment with anastrozole alone or in combination with the PI3K-inhibitor GDC-0941 is designed to test the hypothesis that the combination of estrogen deprivation and PI3K-inhibition has synergistic activity in ER-positive, HER2-negative invasive primary breast cancer. The study will also try to characterize the patient population who might benefit from treatment with PI3K inhibitors and to identify surrogate markers of antitumour effects.

Estrogenblocking drugs such as anastrozole (Arimidex) are often prescribed after breast surgery to prevent disease recurrence. Anastrozole is not effective in all women. GDC0941 is an experimental drug that may help overcome this resistance to anastrozole by inhibiting an enzyme (phosphoinositide3kinase) involved in the mechanisms by which cells ‘talk’ to each other. Before starting large clinical trials we want to confirm the expected short term effects on breast tumour cells and signalling pathways using a modified ‘window of opportunity’ study. This study will guide the development of GDC0941, as it helps understand which breast cancers are likely to benefit.

Window studies are used at early stages of drug development. A sample of a suspected tumour is stored after the diagnostic biopsy. If surgery is required then an experimental drug can be given in the interval between diagnosis and surgery (typically 24 weeks in the NHS). Another sample of the tumour is taken at surgery and compared to the original baseline sample. Window studies allow the initial assessment of a drug with relatively little intrusion into a woman’s progress through the care pathway.

More details can be found at:

Ethics approval

First MREC approval date 17/10/2011, ref.: 11/LO/1559

Study design

Randomised; Interventional; Design type: Treatment

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Topic: National Cancer Research Network; Subtopic: Breast Cancer; Disease: Breast


Breast Tumour Biopsy, Before study treatment and after study treatment during surgery; ECG, Before study treatment and after two weeks of study treatment; Informed Consent, Obtained in writing prior to any protocol specific procedures
Study Treatment, Two weeks of either GDC-0941 and anastrozole or anastrozole alone
Venepuncture, Before study treatment and after two weeks of treatment

Follow Up Length: 2 month(s)

Study Entry : Single Randomisation only

Intervention type



Phase II

Drug names

Anastrazole, PI3K inhibitor GDC0941

Primary outcome measures

Change in Ki67 content of the tumour biopsies; Timepoint(s): Before and after two weeks of treatment

Secondary outcome measures

1. Change in apoptosis in biopsies, plasma biomarkers; Timepoint(s): After two weeks
2. Clinical objective responses, adverse events and vital signs.; Timepoint(s): After two weeks
3. Genetic states of participants in relation to above changes; Timepoint(s): After two weeks

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

Women must meet ALL of the following criteria:
1. Histologically confirmed breast cancer involving a palpable tumour of any size, or a tumour with an ultrasound assessed diameter of ≥ 1.0 cm
2. Estrogen receptor (ER) positive tumours with ≥1% of tumour cells positive for ER on immunohistochemical staining or an immunhistochemistry score (Allred) of 3 or higher
3. No prior systemic treatment regimens for the new primary breast cancer currently under investigation; prior treatment for previous breast cancer is allowed as long as it was completed at least 1 year prior to inclusion into this trial.
4. Postmenopausal, defined as 1) age ≥ 55y and 1y or more of amenorrhea, OR 2) age < 55y and 1y or more of amenorrhea, with an estradiol assay <20 pg/mL, OR 3) age < 55y with prior hysterectomy but intact ovaries with an estradiol level <20 pg/mL, OR
5. Status after bilateral oophorectomy (≥ 28 days prior to first study treatment).
6. Adequate hematologic function (ANC ≥ 1500 cells/μl + platelet count ≥ 100000/μl).
7. Serum creatinine concentration < 1.5 x ULN¿ AST, ALT, bilirubin level < 1.5 x ULN¿ Fasting plasma glucose level < 7.8 mmol/L.
8. ECOG performance status 0-2
9. Written informed consent prior to admission to the study

Participant type


Age group




Target number of participants

Planned Sample Size: 141; UK Sample Size: 141; Description: Postmenopausal women with newly diagnosed, ER-positive, HER2-negative, invasive primary breast cancer of at least 1 cm size.

Participant exclusion criteria

1. Male gender
2. Inflammatory breast cancer.
3. HER2 positive tumours with 3+ intensity on IHC staining for HER2 or amplification of the HER2 gene on ISH.
4. Evidence of distant metastases.
5. Previous systemic or local treatment for the new primary breast cancer currently under investigation (including surgery, radiotherapy, cytotoxic and endocrine treatments); prior treatment for previous breast cancer is allowed as long as it was completed at least 1 year prior to inclusion into this trial.
6. Clinically significant pulmonary dysfunction.
7. Uncontrolled Type 1 or 2 diabetes mellitus (diabetic patients must have been on a stable regimen of oral antihyperglycemic therapy for at least 3 weeks duration and must have home monitoring levels without fasting blood glucose >8.9 mmol/L or hypoglycemia for one week prior to study entry)
8. Serious intercurrent medical or psychiatric illness, including serious active infection.
9. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry.
10. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator’s opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Clinical Investigation and Research Unit
United Kingdom

Sponsor information


Brighton & Sussex University Hospitals NHS Trust (UK)

Sponsor details

Royal Sussex County Hospital
Eastern Road
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Genentech, Inc

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes