Clinical trial NCT01082068 (phase 1/phase 2, status: completed)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: xl147 (sar245408), xl765 (sar245409), letrozole (femara)
SMILES: COC1=CC=C(Cl)C(NC2=C(NS(=O)(=O)C3=CC(NC(=O)C(C)(C)N)=CC=C3)N=C3C=CC=CC3=N2)=C1, CCN1C(=O)C(=CC2=C(C)N=C(N)N=C12)C1=CC=NN1, N#CC1=CC=C(C=C1)C(N1C=NC=N1)C1=CC=C(C=C1)C#N
Eligibility criteria:

        Inclusion Criteria:

          -  The subject has histologically confirmed breast cancer that is ER+ and/or PGR+.

          -  The subject's breast cancer is negative for HER2.

          -  The subject has recurrent or metastatic breast cancer that is refractory to a
             nonsteroidal aromatase inhibitor and has either disease progression or disease
             recurrence.

          -  Subjects previously treated with letrozole must be able to tolerate the approved dose
             and schedule of letrozole.

          -  For subjects enrolled in Phase 2, either archival tumor samples must be available, or
             the subject must be willing to undergo a fresh biopsy.

          -  In Phase 2, at least 30 subjects in each arm must have measurable disease

          -  The subject is a postmenopausal female.

          -  If a subject is currently receiving bisphosphonates, the subject must have received
             the bisphosphonates for at least 2 months before starting study treatment.

          -  The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤
             1.

          -  The subject has adequate organ and marrow function.

          -  The subject has no other diagnosis of malignancy or evidence of other malignancy for 2
             years before screening for this study (except non-melanoma skin cancer or in situ
             carcinoma of the cervix).

          -  The subject is capable of understanding and complying with the protocol requirements
             and has signed the informed consent document.

        Exclusion Criteria:

          -  The subject has received prior treatment with a selective inhibitor of PI3K, AKT,
             and/or mTOR.

          -  Certain restrictions on prior therapies apply.

          -  The subject has not recovered from toxicity due to prior therapy to Grade ≤ 1 or to
             pre-therapy baseline.

          -  The subject has untreated, symptomatic, or progressive brain metastases.

          -  The subject has only non-measurable lesions, other than bone, skin, or chest wall
             metastasis

          -  The subject has to start cytotoxic chemotherapy due to rapid progressive disease
             involving major organs.

          -  The subject 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.

          -  The subject has uncontrolled significant intercurrent illness.

          -  The subject has a baseline corrected QT interval (QTc) > 470 ms.

          -  The subject has a diagnosis of uncontrolled diabetes mellitus.

          -  The subject is known to be positive for the human immunodeficiency virus (HIV).

          -  The subject has a previously identified allergy or hypersensitivity to components of
             the study treatment formulation(s).

          -  The subject is unable or unwilling to abide by the study protocol or cooperate fully
             with the investigator or designee.