Metastatic Breast Cancer
Conditions
Keywords
TDM-1, HER2, HER2+, HER2+ Breast Cancer, HER-2, MBC, Trastuzumab emtansine
Brief summary
This multicenter, Phase Ib study is an open label, dose escalation, three-arm study evaluating the safety, tolerability, pharmacokinetics, and activity of oral (PO) GDC 0941 administered in combination with either intravenous (IV) infusion of T-DM1 or IV infusion of trastuzumab.
Interventions
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented locally advanced or metastatic breast cancer that has progressed on at least one trastuzumab-based regimen in the metastatic or locally advanced setting * HER2-positive disease documented by one of the following results using FDA-approved testing methods: FISH-positive, chromogenic in situ hybridization (CISH)-positive, or IHC 3 + by local laboratory assessment * Life expectancy \>= 90 days * Agreement to use an effective form of contraception for the duration of the study
Exclusion criteria
* History of Grade \>= 3 hypersensitivity reaction to trastuzumab, or Grade \>= 1 with the most recent trastuzumab infusion before study entry, or continued requirement for prolonged trastuzumab infusions to prevent hypersensitivity reactions * History of intolerance to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued * Prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy, hormonal therapy) within 2 weeks prior to Day 1 * Prior investigational anti-cancer therapy within 4 weeks prior to Day 1 * Grade \>= 2 peripheral neuropathy * History of Grade \>= 3 hyperglycemia (fasting) * History of Type 1 or Type 2 diabetes requiring daily medication * History of clinically significant cardiac or pulmonary dysfunction * History of malabsorption syndrome or other condition that would interfere with enteral absorption * Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus * Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytic agents * Any condition requiring \> 2 grams of acetaminophen daily * Need for current chronic corticosteroid therapy * Pregnancy, lactation, or breast-feeding * Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) * Major surgical procedure or significant traumatic injury within 28 days prior to Day 1, or anticipation of the need for major surgery during the course of study treatment * Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy * Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes in cardiac function | Through study completion or early study discontinuation |
| Changes in vital signs, physical findings, and clinical laboratory results during and following administration of study drugs that result in dose modification, dose delay, or discontinuation of T-DM1 and/or GDC 0941 | Through study completion or early study discontinuation |
| Incidence, nature, and severity of adverse events | Through study completion or early study discontinuation |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters of T-DM1 and GDC-0941 (total exposure, maximum serum concentration, and minimum concentration) | Through study completion or early study discontinuation |
| Duration of response | Time from initial complete or partial response to the time of disease progression or death on study |
| Progression-free survival (PFS) | From study treatment initiation to the first occurrence of disease progression or death on study |
| Objective response based on investigator assessment | Confirmed response >/= 4 weeks after initial documentation of response |
Countries
United States
Outcome results
None listed