Primary breast cancer MedDRA version: 14.1 Level: LLT Classification code 10006206 Term: Breast carcinoma NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: GDC-0941
Pharmaceutical Form: Tablet
INN or Proposed INN: GDC-0941
CAS Number: 957054-33-0
Current Sponsor code: GDC-0941
Sponsors
Brighton & Sussex University Hospitals NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Women must meet ALL of the following criteria: • Histologically-confirmed breast cancer involving a palpable tumour of any size, or a tumour with an ultrasound-assessed diameter of = 1.0 cm • 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 • *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.* • Postmenopausal, defined as 1) age = 55y and 1y or more of amenorrhea, OR 2) age =65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: • Male gender • *Inflammatory breast cancer.* • HER2-positive tumours with 3+ intensity on IHC staining for HER2 or amplification of the HER2 gene on ISH. • Evidence of distant metastases. • *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.* •*Previous systemic treatment for other neoplasms within 1 year prior to inclusion into this trial.* • Clinically significant pulmonary dysfunction. • Uncontrolled Type 1 or 2 diabetes mellitus (diabetic patients must have been on a stable regimen of oral anti-hyperglycemic 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) • Serious intercurrent medical or psychiatric illness, including serious active infection. • Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry. • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Change in tumour cell proliferation measured by Ki67 immunohistochemical assessment (%) in biopsy samples taken at diagnosis and day 15.;Timepoint(s) of evaluation of this end point: At baseline and on day 15.; Main Objective: In women with ER-positive breast cancer about to undergo surgery, does two week's pretreatment with a new drug (the PI3K inhibitor GDC-0941, given in combination with the estrogen-blocker anastrozole) increase the benefits of anastrozole in slowing down tumour cell growth, as measured by laboratory measurements on tumour cells? ; Secondary Objective: • Does the new combination kill cancer cells more effectively than anastrozole alone? • Is the new combination more effective than anastrozole alone in shrinking the breast cancer? • Is it possible to link any apparent benefits of using GDC-0941 to the biomarker status of the patient, perhaps leading to a strategy of tailored drug therapy to be examined in future studies? | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary outcome measures for this study are: • Increase in apoptosis: Changes in the tumour (TUNEL assay) measured at diagnosis and on day 15. • Change in tumour cell proliferation after discontinuation of GDC-0941 as measured by Ki67 IHC (%) on day 15 and on the day of definitive surgery *(if surgery is not performed on Day 15 +/- 2 days*) • Clinical objective response. • Pathological response and residual cancer burden. The safety outcome measures for this study are as follows: • Incidence of serious adverse events • Incidence of all adverse events of all grades • Adverse events leading to anastrozole or GDC-0941 discontinuation • Changes in vital signs and clinical laboratory results during and following study drug administration • Changes in ECG measurements Exploratory Outcome Measures Exploratory outcome measures may include genome-wide measurements in tumour DNA and RNA, including mutational status, RNA gene-expression values, DNA copy number, and protein expression and phosphorylation. Exploratory analysis may include, but will not be limited to, the following: • Presence of activating PI3KCA mutations in tumour specimens taken at surgery by PCR and/or sequencing • Level of PTEN expression in tumour biopsy specimens taken at baseline, after 15 (+/-2) days of treatment and at surgery by IHC and/or reverse phase protein array (RPPA) • Level of expression and phosphorylation of candidate proteins (including but not limited to Akt, PTEN, S6, p70S6, PRAS40, EGFR, HER2, HER3, ERK1/2, GSK3ab, ER, MEK1-2, p27, 4EBP1) in tumour biopsy specimens taken at baseline, after 15 (+/-2) days of treatment and at surgery by IHC, reverse-phase protein arrays and/or coincidence detection assay • | — |
Countries
United Kingdom
Contacts
Public ContactTrial Coordinator
Brighton & Sussex University Hospitals NHS Trust
Outcome results
None listed