Clinical trial NCT00928330: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Breast Cancer
Keywords: TDM-1
HER2
HER2+
HER2+ Breast Cancer
HER-2
MBC
Trastuzumab emtansine
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2009-06-25
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility 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

Primary outcomes:
measure: Changes in cardiac function
timeFrame: Through study completion or early study discontinuation
measure: 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
timeFrame: Through study completion or early study discontinuation
measure: Incidence, nature, and severity of adverse events
timeFrame: Through study completion or early study discontinuation
Secondary outcomes:
measure: PK parameters of T-DM1 and GDC-0941 (total exposure, maximum serum concentration, and minimum concentration)
timeFrame: Through study completion or early study discontinuation
measure: Progression-free survival (PFS)
timeFrame: From study treatment initiation to the first occurrence of disease progression or death on study
measure: Objective response based on investigator assessment
timeFrame: Confirmed response >/= 4 weeks after initial documentation of response
measure: Duration of response
timeFrame: Time from initial complete or partial response to the time of disease progression or death on study
Other outcomes:
Locations:
city: Indianapolis
country: United States
state: Indiana
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: