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

Genentech

Status and phase: Completed; Phase 1

Conditions: Metastatic Breast Cancer

Treatments: Drug: GDC-0941; Drug: Trastuzumab; Drug: trastuzumab-MCC-DM1

Study type: Interventional

Funder types: Industry

Identifiers

NCT00928330

GO01302 (Other Identifier)

GDC4627g

Details and patient eligibility

About

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.

Enrollment: 57 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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57 participants in 3 patient groups

A

Experimental group

Treatment:

Drug: trastuzumab-MCC-DM1

Drug: GDC-0941

B

Experimental group

Treatment:

Drug: trastuzumab-MCC-DM1

Drug: GDC-0941

C

Experimental group

Treatment:

Drug: GDC-0941

Drug: Trastuzumab