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.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT00928330
First received: June 23, 2009
Last updated: July 21, 2014
Last verified: July 2014

June 23, 2009
July 21, 2014
July 2009
January 2014   (final data collection date for primary outcome measure)
  • 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 ]
  • Changes in cardiac function [ Time Frame: 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 [ Time Frame: Through study completion or early study discontinuation ]
  • Incidence, nature, and severity of adverse events [ Time Frame: Through study completion or early study discontinuation ]
Complete list of historical versions of study NCT00928330 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
  • Progression-free survival (PFS) [ Time Frame: From study treatment initiation to the first occurrence of disease progression or death on study ]
  • Objective response based on investigator assessment [ Time Frame: Confirmed response ≥ 4 weeks after initial documentation of response ]
  • Duration of response [ Time Frame: Time from initial complete or partial response to the time of disease progression or death on study ]
Not Provided
Not Provided
 
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 st udy 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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic Breast Cancer
  • Drug: GDC-0941
    Oral repeating dose
  • Drug: trastuzumab-MCC-DM1
    Intravenous repeating dose
  • Drug: Trastuzumab
    Intravenous repeating dose
  • Experimental: A
    Interventions:
    • Drug: GDC-0941
    • Drug: trastuzumab-MCC-DM1
  • Experimental: B
    Interventions:
    • Drug: GDC-0941
    • Drug: trastuzumab-MCC-DM1
  • Experimental: C
    Interventions:
    • Drug: GDC-0941
    • Drug: Trastuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
57
January 2014
January 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00928330
GDC4627g, GO01302
Not Provided
Genentech
Genentech
Not Provided
Study Director: Clinical Trials Genentech
Genentech
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP