A Study of PI3-Kinase Inhibitor GDC-0941 in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole, in Participants With Locally Recurrent or Metastatic Breast Cancer

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of PI3-Kinase Inhibitor GDC-0941 (Pictilisib) in Combination With Paclitaxel, With and Without Bevacizumab or Trastuzumab, and With Letrozole in Patients With Locally Recurrent Or Metastatic Breast Cancer

This is an open-label, multicenter, Phase Ib dose-escalation study to assess the safety, tolerability, and pharmacokinetics of oral (PO) pictilisib administered with letrozole or intravenous (IV) paclitaxel with and without IV bevacizumab or IV trastuzumab in participants with locally recurrent or metastatic breast cancer. The study consists of three parts. Part 1 (pictilisib will be administered in 21+7 schedule along with paclitaxel and/or bevacizumab), Part 2 (pictilisib will be administered in 5+2 schedule along with paclitaxel and/or bevacizumab or trastuzumab) and Part 3 (pictilisib will be administered in combination with letrozole). Part 1 and Part 2 consists of two stages; a dose escalation stage and a cohort-expansion stage.

Inclusion Criteria:

• Confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease
• Adequate organ and bone marrow function as assessed by laboratory tests
• Evaluable disease or disease measurable per RECIST
• Agreement to use an effective form of contraception for the duration of the study

Exclusion Criteria:

• History of malabsorption syndrome or other condition that would interfere with enteral absorption
• Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents
• Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, radiotherapy, or hormonal therapy) within 4 weeks or 5 half-lives (whichever is shorter) of the first dose of study treatment
• Uncontrolled current illness
• Active small or large intestine inflammation (such as Crohn's disease or ulcerative colitis)
• Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
• Known HIV infection
• New York Heart Association (NYHA) Class II or greater congestive heart failure
• Active ventricular arrhythmia requiring medication
• Pregnancy, lactation, or breastfeeding
• Known significant hypersensitivity to study drugs or excipients
• History of arterial thromboembolic disease within 6 months of first study treatment
• No more than two prior chemotherapy regimens for metastatic disease