University of Southern California
USC Norris Comprehensive Cancer Center
If you are a patient, please contact Keck Medical Center of USC at 800-USC-CARE.

Trial 1B-10-8

A Phase I/II Dose-Escalation Study of XL147 or XL765 in Combination with Letrozole in Subjects with Hormone Receptor-Positive and HER2-Negative Breast Cancer Refractory to a Non-Steroidal Aromatase Inhibitor.

Type: Treatment
Phase: Phase I/II
Status: Not Open (Closed)
Treatments: Chemotherapy: Systemic
Randomized: No
Defintions of terms and FAQ about clinical trials.
Trial Leaders/Researchers:  Agustin Garcia, M.D.
Other Trial Staff:  Kristy Watkins, R.N., Nancy Perez, R.N., Yvonne Flores, D.M., Anayansi Miloud, D.M.

Staff may log in to see study documents.

You may participate in this study if:
1Histologically confirmed breast cancer that is ER+ and/or PGR+
2Negative for HER2 overexpression by IHC or for HER2 gene amplification by fluorescent in-situ hybridization (FISH) or equivalent method
3Recurrent or metastatic breast cancer that is refractory to a non-steroidal aromatase inhibitor
4For subjects enrolled in Phase II of both treatment arms: [a] At least fifteen 4-10 micron tumor tissue sections (at least 15 unstained slides, 20 preferably, without cover slips), or a tissue block of the subject’s tumor should be identified, be in the possession of the participating site/institution, and be designated for shipment to the sponsor. [b] Fresh tumor biopsies obtained prior to day 1 of treatment are required for at least 15 subjects in each arm.
5At least 30 subjects in each arm (Phase II) must have measurable disease
6Post-menopausal female at least 18 years of age
7ECOG performance status of < / = 1
8AGC = / > 1.5; platelets = / > 100,000; Hgb = / > 9.0
9Bilirubin < / = 1.5 x uln; SGOT & SGPT < / = 2.5 x uln
10Creatinine < / = 1.5 x uln or calculated creatinine clearance = / > 60 ml/min
11PT/ INR or PTT < / = 1.3 x uln
12If currently receiving bisphosphonates, the subject must have received the bisphosphonates for at least 2 months before starting study treatment
13Subjects previously treated with letrozole must be able to tolerate the approved dose and schedule of letrozole
14No 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)
15Signed an approved study-specific informed consent and HIPAA

You may not participate in this study if:
1Prior treatment with a selective inhibitor of PI3K, AKT, and/or mTOR (investigational or approved agents).
2Prior therapy, including [a] small molecule targeted (non-cytotoxic) inhibitors (including investigational kinase inhibitors) within 2 weeks or 5 half-lives of the compound or active metabolites, whichever is longer, before the first dose of study treatment; [b] RT within 2 weeks before the first dose of study treatment; [c] hormonal therapy (other than non-steroidal aromatase inhibitors) within 2 weeks before the first dose of study treatment; [d] cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks, or nitrosoureas or mitomycin C within 6 weeks before the first dose of study treatment; [e] biologic therapy (including antibodies, immune modulators, cytokines) within 4 weeks before the first dose of study treatment; [f] any other type of investigational agent within 4 weeks before the first dose of study treatment; [g] major surgery, or not recovered from major surgery, within 4 weeks before the first dose of study treatment.
3Must have received no more than two prior cytotoxic chemotherapeutic regimens for metastatic breast cancer
4Has not recovered from toxicity due to prior therapy to Grade < / = 1 or to pre-therapy baseline. Subjects with Grade 2 peripheral neuropathy or Grade 2 alopecia related to prior therapies are eligible.
5Subject has only non-measurable lesions other than bone, skin, or chest wall metastasis (e.g., pleural effusion, ascites, others).
6Untreated, symptomatic, or progressive brain metastases
7Subject has to start cytotoxic chemotherapy due to rapid PD involving major organs
8Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, clinically significant cardiac arrhythmias, hypertension, or any of the following within 3 months: [a] symptomatic CHF; [b] unstable angina pectoris; [c] stroke; [d] MI
9Baseline corrected QT interval (QTc) >470 ms
10Diagnosis of uncontrolled DM
11Prior hormone replacement therapy within 14 days of the start of study treatment or may need to initiate hormone replacement therapy during the study
12Known to be positive for HIV
13Previously identified allergy or hypersensitivity to components of the study treatment formulation
14Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee

For further information on a study, please contact the Clinical Investigation Support Office at (323) 865-0451, or

To schedule a consultation with the hospital, please call our New Patient Referrals Office at (323) 865-3111.