A trial looking at GDC0941 and anastrozole for oestrogen positive breast cancer (OPPORTUNE)

Phase 2

Completed

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

• Registration Number: ISRCTN26131497
• Lead Sponsor: Brighton & Sussex University Hospitals NHS Trust (UK)

Brief Summary

2016 results in https://www.ncbi.nlm.nih.gov/pubmed/26976426

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-02-18
• Study Completion: 2017-12-31
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Completed
• Sex: Female
• Target Recruitment: 141

Inclusion 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,
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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> Change in Ki67 content of the tumour biopsies; Timepoint(s): Before and after two weeks of treatment.<br><br> Added 28/02/2017:<br> Change in tumour cell proliferation measured by Ki67 immunohistochemical assessment (%) in biopsy samples taken at diagnosis and day 15.<br>

Secondary Outcome Measures

Name	Time	Method
<br> 1. Change in apoptosis in biopsies, plasma biomarkers; Timepoint(s): After two weeks<br> 2. Clinical objective responses, adverse events and vital signs.; Timepoint(s): After two weeks<br> 3. Genetic states of participants in relation to above changes; Timepoint(s): After two weeks<br><br> Added 28/02/2017:<br> 1. Change in apoptosis in biopsies are assessed by changes in the tumour (TUNEL assay) at diagnosis and day 15<br> 2. Tumour cell proliferation after discontinuation of GDC-0941 as measured by Ki67 IHC (%) on day 15 and the day of surger (anastrozole+GDC-0941 arm only)<br> 3. Clinical objective responses, adverse events and vital signs at diagnosis and day 15<br> 4. Pathological response and residual cancer burden<br>