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

A Phase Ib, Open-Label Study of the Safety, Tolerability, Pharmacokinetics, and Activity of 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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: GDC-0941; Drug: trastuzumab-MCC-DM1; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
  • Maryland
    • Baltimore, Maryland, United States, 21231
  • Massachusetts
    • Boston, Massachusetts, United States, 02115

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: GDC-0941; Oral repeating dose; Drug: trastuzumab-MCC-DM1; Intravenous repeating dose
Experimental: B	Drug: GDC-0941; Oral repeating dose; Drug: trastuzumab-MCC-DM1; Intravenous repeating dose
Experimental: C	Drug: GDC-0941; Oral repeating dose; Drug: Trastuzumab; Intravenous repeating dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence, nature, and severity of adverse events	Through study completion or early study discontinuation
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

Secondary Outcome Measures

Outcome 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
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
Duration of response	Time from initial complete or partial response to the time of disease progression or death on study

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: June 23, 2009
• First Submitted That Met QC Criteria: June 24, 2009
• First Posted (Estimate): June 25, 2009

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: HER2; HER-2; MBC; HER2+; Trastuzumab emtansine; HER2+ Breast Cancer; TDM-1
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Trastuzumab; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: GDC4627g; GO01302 (Other Identifier: Hoffmann-La Roche)