Trastuzumab and Trastuzumab-MCC-DM1 Administered Intravenously and GDC-0941 Administered Orally to Patients With HER2-Positive Metastatic Breast Cancer Who Have Progressed on Previous Trastuzumab-Based Therapy

• Status: Completed
• Trial end date: 2014-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genentech, Inc.
• Treatments: Ado-Trastuzumab Emtansine; Maytansine; Trastuzumab

Criteria

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