- Minimum age for inclusion 18 years and a WHO performance status 2
- Patients with metastatic or incurable locally advanced disease
- Female patients with Breast cancer patients with ER and/or PR positive tumours In the
phase 1b part of the study, breast cancer patients may have either HER2 negative or
HER2 positive disease.
- Patients with other cancer types are eligible if the investigator considers that they
might benefit from endocrine therapy combined with PI3K inhibition
- During the dose escalation phase 1b, patients may have either measurable or
non-measurable disease by RECIST criteria
- Archival tumour tissue is allowed, however fresh biopsies are desirable whenever
feasible and accessible according to the investigator's judgment
- Life expectancy 12 weeks.
- adequate organ and marrow function
- understanding and complying with the protocol requirements and has signed the
informed consent document.
- child bearing potential must have a negative serum or urine pregnancy test within 14
days prior to registration/randomisation, and must use an effective method of
contraception during treatment and for at least 60 days after the final dose of study
- The following restrictions on prior anticancer therapy apply;
- Endocrine therapies or small molecule targeted (non-cytotoxic) inhibitors within 2
weeks or 5 half-lives of the compound or active metabolites, whichever is longer,
before the first dose of the study treatment are not allowed
--No more than 5 prior chemotherapeutic regimens for metastatic breast cancer
- Radiation therapy within 2 weeks before the first dose of study treatment, unless of
palliative intent, not compromising bone marrow function
- Cytotoxic chemotherapy within 3 weeks, or nitrosoureas or mitomycin C within 6 weeks
before the first dose of the study treatment
- Antibody therapy within 4 weeks before the first dose of the study treatment
- Major surgery or not recovered from major surgery, within 4 weeks before the first
dose of study treatment
- Other malignancy with the exclusion of carcinoma in situ.
- The patient has not recovered from toxicity due to prior therapy to grade 1 or to
pre-therapy baseline. Patients with grade 2 peripheral neuropathy or grade 2 alopecia
related to prior therapies are eligible
- The patient has untreated, symptomatic, or progressive brain metastases. -The patient
has a history of thrombo-embolic disease or is currently receiving anticoagulation
with therapeutic doses of warfarin.
- The patient has prothrombin time/ International Normalized Ratio (PT/ INR) or partial
thromboplastin time (PTT) test results at screening that are above 1.3 x the
laboratory upper limit of normal.
- Patients with a history of Crohn's disease or ulcerative colitis or other forms of
- The patient has uncontrolled significant intercurrent illness
- History of clinically significant cardiac or pulmonary dysfunction-The patient has a
type 1 or 2 diabetes requiring daily antihyperglycemic medication
- Corticosteroid use equivalent to more than 10mg prednisone daily
- The patient is known to be positive for the human immunodeficiency virus (HIV).
- The patient has a previously identified allergy or hypersensitivity to components of
the study treatment formulation(s).
- The patients is unable or unwilling to abide by the study protocol or cooperate fully
with the investigator or designee
- Pregnant or nursing women
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Female