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A Phase 1/2 Dose-Escalation Study of XL147 (SAR245408) or XL765 (SAR245409) in Combination With Letrozole in Subjects With Hormone Receptor-Positive and HER2-Negative Breast Cancer Refractory to a Nonsteroidal Aromatase Inhibitor

Phase 1/Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Phase 1/2 Dose-Escalation Study of XL147 (SAR245408) or XL765 (SAR245409) in Combination With Letrozole in Subjects With Hormone Receptor-Positive and HER2-Negative Breast Cancer Refractory to a Nonsteroidal Aromatase Inhibitor

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

- 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 ≤

- 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and tolerability of XL147 and letrozole and XL765 and letrozole

Outcome Time Frame:

at weekly and bi-weekly study visits

Safety Issue:


Principal Investigator

Clinical Sciences & Operations

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

June 2010

Completion Date:

March 2013

Related Keywords:

  • Breast Cancer
  • HER2 negative
  • Hormone Receptor Positive
  • Breast Neoplasms
  • Breast Neoplasms



Investigational Site Number 1214 Nashville, Tennessee  37203
Investigational Site Number 1537 Los Angeles, California  90033
Investigational Site Number 1238 Fort Meyers, Florida  33901
Investigational Site Number 1138 Boston, Massachusetts  02115
Investigational Site Number 1330 Detroit, Michigan  48201
Investigational Site Number 1441 Chicago, Illinois  60611
Investigational Site Number 1331 Ann Arbor, Michigan  48109
Investigational Site Number 5201 Columbia, Missouri  65201
Investigational Site Number 1252 Durham, North Carolina  27710
Investigational Site Number 5246 El Paso, Texas  79915
Investigational Site Number 1601 Denver, Colorado  80262