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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 study has been completed.
Information provided by (Responsible Party):
Genentech, Inc. Identifier:
First received: June 23, 2009
Last updated: February 4, 2015
Last verified: February 2015

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.

Condition Intervention Phase
Metastatic Breast Cancer
Drug: GDC-0941
Drug: Trastuzumab
Drug: trastuzumab-MCC-DM1
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Changes in cardiac function [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
  • Incidence, nature, and severity of adverse events [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PK parameters of T-DM1 and GDC-0941 (total exposure, maximum serum concentration, and minimum concentration) [ Time Frame: Through study completion or early study discontinuation ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: From study treatment initiation to the first occurrence of disease progression or death on study ] [ Designated as safety issue: No ]
  • Objective response based on investigator assessment [ Time Frame: Confirmed response >/= 4 weeks after initial documentation of response ] [ Designated as safety issue: No ]
  • Duration of response [ Time Frame: Time from initial complete or partial response to the time of disease progression or death on study ] [ Designated as safety issue: No ]

Enrollment: 57
Study Start Date: July 2009
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00928330

United States, Indiana
Indianapolis, Indiana, United States, 46202
United States, Maryland
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Genentech, Inc.
Study Director: Clinical Trials Genentech, Inc.
  More Information

No publications provided

Responsible Party: Genentech, Inc. Identifier: NCT00928330     History of Changes
Other Study ID Numbers: GDC4627g, GO01302
Study First Received: June 23, 2009
Last Updated: February 4, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech, Inc.:
HER2+ Breast Cancer
Trastuzumab emtansine

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Ado-trastuzumab emtansine
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Tubulin Modulators processed this record on February 27, 2015